Publications by authors named "Chris Kong Chu Wong"

43 Publications

Characterization of PFOS toxicity on in-vivo and ex-vivo mouse pancreatic islets.

Environ Pollut 2021 Jul 26;289:117857. Epub 2021 Jul 26.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Considerable human data have shown that the exposure to perfluorooctane sulfonate (PFOS) correlates to the risk of metabolic diseases, however the underlying effects are not clearly elucidated. In this study, we investigated the impacts of PFOS treatment, using in-vivo, ex-vivo and in-vitro approaches, on pancreatic β-cell functions. Mice were oral-gavage with 1 and 5 μg PFOS/g body weight/day for 21 days. The animals showed a significant increase in liver triglycerides, accompanied by a reduction of triglycerides in blood sera and glycogen in livers and muscles. Histological examination of pancreases showed no noticeable changes in the size and number of islets from the control and treatment groups. Immunohistochemistry showed a reduction of staining intensities of insulin and the transcriptional factors (Pdx-1, islet-1) in islets of pancreatic sections from PFOS-treated groups, but no changes in the intensity of Glut2 and glucagon were noted. Transcriptomic study of isolated pancreatic islets treated ex vivo with 1 μM and 10 μM PFOS for 24 h, underlined perturbations of the insulin signaling pathways. Western blot analysis of ex-vivo PFOS-treated islets revealed a significant reduction in the expression levels of the insulin receptor, the IGF1 receptor-β, Pdk1-Akt-mTOR pathways, and Pdx-1. Using the mouse β-cells (Min-6) treated with 1 μM and 10 μM PFOS for 24 h, Western blot analysis consistently showed the PFOS-treatment inhibited Akt-pathway and reduced cellular insulin contents. Moreover, functional studies revealed the inhibitory effects of PFOS on glucose-stimulated insulin-secretion (GSIS) and the rate of ATP production. Our data support the perturbing effects of PFOS on animal metabolism and demonstrate the underlying molecular targets to impair β-cell functions.
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http://dx.doi.org/10.1016/j.envpol.2021.117857DOI Listing
July 2021

Bisphenol A and its analogues in sedimentary microplastics of Hong Kong.

Mar Pollut Bull 2021 Mar 30;164:112090. Epub 2021 Jan 30.

Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Guilin 541004, PR China; Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin 541004, PR China; Department of Chemistry, City University Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

The occurrence and spatial distribution of bisphenol A (BPA) and analogues bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS) were investigated in microplastic on 11 beaches in Hong Kong. At 10 sites, BPA was the only detected chemical with concentrations ranged from 82.4-989 ng g microplastic. BPA, BPB and BPS co-occurred at only one site, where it is located close proximity to the outfall of a sewage treatment plant. There was no significant spatial difference of BPA concentrations in microplastic when all the sites were considered, indicating that some remote and presumably cleaner beaches have been contaminated. PE, PP and PS (represented >90% of total polymers) were the most dominated polymers, but there was no correlation between polymer types and BPA concentrations. No evidence was found that the BPA and its analogues accumulate on microplastic since the concentrations were comparable to those found in the sediment.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112090DOI Listing
March 2021

Effects of Exposure to Perfluorooctane Sulfonate on Placental Functions.

Environ Sci Technol 2020 12 1;54(24):16050-16061. Epub 2020 Dec 1.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.

Perfluorooctane sulfonate (PFOS) is a metabolic-disrupting chemical. There is a strong association between maternal and cord blood PFOS concentrations, affecting metabolism in early life. However, the underlying effects have not been fully elucidated. In this study, using the maternal-fetal model, we investigated the impact of gestational PFOS exposure on the placental structure and nutrient transport. Pregnant mice were oral gavaged with PFOS (1 or 3 μg PFOS/g body weight) from gestational day (GD) 4.5 until GD 17.5. Our data showed a significant reduction in fetal body weight at high dose exposure. There were no noticeable changes in placental weights and the relative areas of junctional and labyrinth zones among the control and exposed groups. However, a placental nutrient transport assay showed a significant reduction in maternal-fetal transport of the glucose and amino acid analogues. Western blot analysis showed a significant decrease in the expression levels of placental SNAT4 upon PFOS exposure. Moreover, in the high-dose exposed group, placenta and fetal livers were found to have significantly higher corticosterone levels, a negative regulator of fetal growth. The perturbation in the placental transport function and corticosterone levels accounted for the PFOS-induced reduction of fetal body weights.
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http://dx.doi.org/10.1021/acs.est.0c06569DOI Listing
December 2020

Cadmium induces epithelial-mesenchymal transition and migration of renal cancer cells by increasing PGE2 through a cAMP/PKA-COX2 dependent mechanism.

Ecotoxicol Environ Saf 2021 Jan 30;207:111480. Epub 2020 Oct 30.

School of Life Sciences, Jiangsu University, Jiangsu, Zhenjiang 212000, China. Electronic address:

Environmental or occupational exposure of Cadmium (Cd) is concerned to be a threat to human health. The kidney is main target of Cd accumulation, which increases the risk of renal cell carcinoma (RCC). In addition, low content of Cd had been determined in kidney cancer, however, the roles of presence of Cd in renal tumors progression are still unclear. The present study is proposed to determine the effect of low-dose Cd exposure on the renal cancer cells and aimed to clarify the underlying mechanisms. The cell viability, cytotoxicity, and the migratory effect of low-dose Cd on the renal cancer cells were detected. Moreover, the roles of reactive oxygen species (ROS), Ca, and cyclic AMP (cAMP)/protein kinase A (PKA)-cyclooxygenase2 (COX2) signaling, as well as COX2 catalytic product prostaglandin E2 (PGE2) on cell migration and invasion were identified. Our results suggested that low dose Cd exposure promoted migration of renal cancer Caki-1 cells, which was not dependent on Cd-induced ROS and intracellular Ca levels. Cd exposure induced cAMP/PKA-COX2, which mediated cell migration and invasion, and decreased expressions of epithelial-mesenchymal transition (EMT) marker, E-cadherin, but increased expressions of N-cadherin and Vimentin. Moreover, Cd-induced secretion of PGE2 feedback on activation of cAMP/PKA-COX2 signaling, also promoted EMT, migration and invasion of renal cancer Caki-1 cells. This study might contribute to understanding of the mechanism of Cd-induce progression of renal cancer and future studies on the prevention and therapy of renal cell carcinomas.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111480DOI Listing
January 2021

An Essential and Cell-Cycle-Dependent ORC Dimerization Cycle Regulates Eukaryotic Chromosomal DNA Replication.

Cell Rep 2020 03;30(10):3323-3338.e6

Division of Life Science, Center for Cancer Research, and State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; The First Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, China; EnKang Pharmaceuticals Limited, Guangzhou, China. Electronic address:

Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), completing replication licensing. However, how an asymmetric single-heterohexameric ORC structure loads the symmetric MCM (minichromosome maintenance) double hexamers is controversial, and importantly, it remains unknown when and how ORC proteins associate with the newly replicated origins to protect them from invasion by histones. Here, we report an essential and cell-cycle-dependent ORC "dimerization cycle" that plays three fundamental roles in the regulation of DNA replication: providing a symmetric platform to load the symmetric pre-RCs, marking and protecting the nascent sister replication origins for the next licensing, and playing a crucial role to prevent origin re-licensing within the same cell cycle.
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http://dx.doi.org/10.1016/j.celrep.2020.02.046DOI Listing
March 2020

Genome-wide analysis of MicroRNA-messenger RNA interactome in ex-vivo gill filaments, Anguilla japonica.

BMC Genomics 2020 Mar 4;21(1):208. Epub 2020 Mar 4.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Kowloon Tong, HKSAR, Hong Kong.

Background: Gills of euryhaline fishes possess great physiological and structural plasticity to adapt to large changes in external osmolality and to participate in ion uptake/excretion, which is essential for the re-establishment of fluid and electrolyte homeostasis. The osmoregulatory plasticity of gills provides an excellent model to study the role of microRNAs (miRs) in adaptive osmotic responses. The present study is to characterize an ex-vivo gill filament culture and using omics approach, to decipher the interaction between tonicity-responsive miRs and gene targets, in orchestrating the osmotic stress-induced responses.

Results: Ex-vivo gill filament culture was exposed to Leibovitz's L-15 medium (300 mOsmol l) or the medium with an adjusted osmolality of 600 mOsmol l for 4, 8 and 24 h. Hypertonic responsive genes, including osmotic stress transcriptional factor, Na/Cl-taurine transporter, Na/H exchange regulatory cofactor, cystic fibrosis transmembrane regulator, inward rectifying K channel, Na/K-ATPase, and calcium-transporting ATPase were significantly upregulated, while the hypo-osmotic gene, V-type proton ATPase was downregulated. The data illustrated that the ex-vivo gill filament culture exhibited distinctive responses to hyperosmotic challenge. In the hyperosmotic treatment, four key factors (i.e. drosha RNase III endonuclease, exportin-5, dicer ribonuclease III and argonaute-2) involved in miR biogenesis were dysregulated (P < 0.05). Transcriptome and miR-sequencing of gill filament samples at 4 and 8 h were conducted and two downregulated miRs, miR-29b-3p and miR-200b-3p were identified. An inhibition of miR-29b-3p and miR-200b-3p in primary gill cell culture led to an upregulation of 100 and 93 gene transcripts, respectively. Commonly upregulated gene transcripts from the hyperosmotic experiments and miR-inhibition studies, were overlaid, in which two miR-29b-3p target-genes [Krueppel-like factor 4 (klf4), Homeobox protein Meis2] and one miR-200b-3p target-gene (slc17a5) were identified. Integrated miR-mRNA-omics analysis revealed the specific binding of miR-29b-3p on Klf4 and miR-200b-3p on slc17a5. The target-genes are known to regulate differentiation of gill ionocytes and cellular osmolality.

Conclusions: In this study, we have characterized the hypo-osmoregulatory responses and unraveled the modulation of miR-biogenesis factors/the dysregulation of miRs, using ex-vivo gill filament culture. MicroRNA-messenger RNA interactome analysis of miR-29b-3p and miR-200b-3p revealed the gene targets are essential for osmotic stress responses.
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http://dx.doi.org/10.1186/s12864-020-6630-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057501PMC
March 2020

Comparative Analysis of PFOS and PFOA Toxicity on Sertoli Cells.

Environ Sci Technol 2020 03 6;54(6):3465-3475. Epub 2020 Mar 6.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Hong Kong SAR, P. R. China.

Perfluoroalkyl chemicals induce male reproductive toxicity. Current evidence showed the effects of the chemical exposure on the deterioration of testicular functions, and reduction in epididymal sperm counts. Previous studies showed that PFOA and PFOS displayed a high correlation with each other in seminal plasma levels, but induced different effects on semen variables. In this study, we focused on the comparative toxicity analysis of PFOA and PFOS, using a rat primary Sertoli cell model. Our transcriptomic data showed that PFOA and PFOS treatments (40 μM) perturbed global gene expression. While PFOS induced higher toxicity in affecting cytoskeleton signaling, Sertoli cell-cell junction, and inflammation, underlined by Ingenuity pathway analysis. Immunocytochemical staining revealed that PFOS treatment (40 and 80 μM) induced truncated actin filament and disorganized bundled configuration in the cell cytoplasm. Moreover, disorganized distribution of N-cadherin (N-cad) and β-catenin (β-cat), and defragmentation of ZO-1 at the Sertoli cell-cell interface was evident. At 80 μM of PFOS, cytoplasmic distribution of N-cad, β-cat, and ZO-1 were observed. We then examined whether resveratrol, a polyphenol antioxidant, was able to protect the cells from PFOS toxicity. The pretreatment of Sertoli cells with 10 μM resveratrol prevented the formation of truncated actin filament and dis-localization of β-cat. Western blot analysis showed that Res pretreatment increased the levels of basal ES proteins (N-cad and β-cat), tight junction proteins (ZO-1 and occludin), and gap junction protein, versus control.
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http://dx.doi.org/10.1021/acs.est.0c00201DOI Listing
March 2020

The roles of calcium-sensing receptor (CaSR) in heavy metals-induced nephrotoxicity.

Life Sci 2020 Feb 23;242:117183. Epub 2019 Dec 23.

Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address:

The kidney is a vital organ responsible for regulating water, electrolyte and acid-base balance as well as eliminating toxic substances from the blood in the body. Exposure of humans to heavy metals in their natural and occupational environments, foods, water, and drugs has serious implications on the kidney's health. The accumulation of heavy metals in the kidney has been linked to acute or chronic renal injury, kidney stones or even renal cancer, at the expense of expensive treatment options. Therefore, unearthing novel biomarkers and potential therapeutic agents or targets against kidney injury for efficient treatment are imperative. The calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR) is typically expressed in the parathyroid glands and renal tubules. It modulates parathyroid hormone secretion according to the serum calcium (Ca) concentration. In the kidney, it modulates electrolyte and water excretion by regulating the function of diverse tubular segments. Notably, CaSR lowers passive and active Ca reabsorption in distal tubules, which facilitates phosphate reabsorption in proximal tubules and stimulates proton and water excretion in collecting ducts. Moreover, at the cellular level, modulation of the CaSR regulates cytosolic Ca levels, reactive oxygen species (ROS) generation and the mitogen-activated protein kinase (MAPK) signaling cascades as well as autophagy and the suppression of apoptosis, an effect predominantly triggered by heavy metals. In this regard, we present a review on the CaSR at the cellular level and its potential as a therapeutic target for the development of new and efficient drugs against heavy metals-induced nephrotoxicity.
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http://dx.doi.org/10.1016/j.lfs.2019.117183DOI Listing
February 2020

Calcimimetic compound NPS R-467 protects against chronic cadmium-induced mouse kidney injury by restoring autophagy process.

Ecotoxicol Environ Saf 2020 Feb 9;189:110052. Epub 2019 Dec 9.

Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212000, China. Electronic address:

In the kidney, disturbance of calcium homeostasis can cause renal hemodynamic changes, leading to glomerulonephritis, tubular damage and renal vascular disease, and thus promotes the development of chronic kidney disease (CKD). Cadmium (Cd) is a toxic heavy metals proved to induce disturbances of calcium homeostasis and nephrotoxicity. Calcium sensing receptor (CaSR) is abundantly expressed in the kidney and plays an important role in maintaining body calcium homeostasis. Our previous study suggested that the activation of CaSR could act as a protective pathway to reduce Cd-induced cytotoxicity in renal proximal tubular cells. However, its application in animal models, its treatment efficacy and underlying mechanisms are still unclear. Therefore, an in vivo animal model (ICR male mouse, n = 5) subjected to Cd-induced nephrotoxicity was used in this study. In the present study, the results indicated that long-term (4 weeks) but not short-term (7 days) Cd exposure induced kidney injury, including induced glomerular atrophy, renal proximal tubule damage, increased malondialdehyde (MDA) level, elevated urine protein quantity, and upregulated kidney injury molecule 1 (KIM-1). It was further observed that chronic Cd exposure induced inhibition of autophagy flux, which triggered kidney apoptosis and injury. However, NPS R-467 restored Cd-inhibited autophagy flux and reduced Cd-induced kidney apoptosis and injury. Finding from this study indicated that activation of CaSR in prevention from nephrotoxicity and kidney injury caused by Cd, which might be helpful for the treatment of clinical CKD.
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http://dx.doi.org/10.1016/j.ecoenv.2019.110052DOI Listing
February 2020

Inhibition of Autophagy Alleviates Cadmium-Induced Mouse Spleen and Human B Cells Apoptosis.

Toxicol Sci 2019 07;170(1):109-122

Institute of Life Sciences, Jiangsu University.

Cadmium (Cd) is a toxic heavy metal that can accumulate and cause severe damage to many organs, such as liver, kidney, lung, etc. Cd also significantly suppresses immunity, however, the underlying mechanism involved in Cd-induced immunnotoxicity is still unclear. The present study indicated that semichronic Cd exposure (7 days) induced apoptotic damage of mouse spleen. In human Ramos B cells, Cd exposure also induced apoptosis, which was dependent on Cd-induced vacuole membrane protein 1 (VMP1) expression and autophagy. Cd-induced autophagy and apoptosis were abated when VMP1 expression was knockdown. In addition, Cd-induced VMP1 expression, autophagy, and apoptosis were dependent on the elevation of Ca2+ and reactive oxygen species (ROS). More important, Cd exposure also induced VMP1 expression and autophagy in mouse spleen tissue, and the intraperitoneal injection of the autophagy inhibitor chloroquine (CQ) into mice effectively reduced Cd-induced spleen apoptotic damage. Taken together, these results indicate Cd-induced autophagy, promotes apoptosis in immune cells, and inhibition of autophagy can alleviate Cd-induced spleen and immune cell apoptosis. This study might provide the groundwork for future studies on Cd-induced immunomodulatory effects and immune diseases.
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http://dx.doi.org/10.1093/toxsci/kfz089DOI Listing
July 2019

Dietary Exposure to the Environmental Chemical, PFOS on the Diversity of Gut Microbiota, Associated With the Development of Metabolic Syndrome.

Front Microbiol 2018 24;9:2552. Epub 2018 Oct 24.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

The gut microbiome is a dynamic ecosystem formed by thousands of diverse bacterial species. This bacterial diversity is acquired early in life and shaped over time by a combination of multiple factors, including dietary exposure to distinct nutrients and xenobiotics. Alterations of the gut microbiota composition and associated metabolic activities in the gut are linked to various immune and metabolic diseases. The microbiota could potentially interact with xenobiotics in the gut environment as a result of their board enzymatic capacities and thereby affect the bioavailability and toxicity of the xenobiotics in enterohepatic circulation. Consequently, microbiome-xenobiotic interactions might affect host health. Here, we aimed to investigate the effects of dietary perfluorooctane sulfonic acid (PFOS) exposure on gut microbiota in adult mice and examine the induced changes in animal metabolic functions. In mice exposed to dietary PFOS for 7 weeks, body PFOS and lipid contents were measured, and to elucidate the effects of PFOS exposure, the metabolic functions of the animals were assessed using oral glucose-tolerance test and intraperitoneal insulin-tolerance and pyruvate-tolerance tests; moreover, on Day 50, cecal bacterial DNA was isolated and subject to 16S rDNA sequencing. Our results demonstrated that PFOS exposure caused metabolic disturbances in the animals, particularly in lipid and glucose metabolism, but did not substantially affect the diversity of gut bacterial species. However, marked modulations were detected in the abundance of metabolism-associated bacteria belonging to the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Cyanobacteria, including, at different taxonomic levels, , and . The results of PICRUSt analysis further indicated that PFOS exposure perturbed gut metabolism, inducing notable changes in the metabolism of amino acids (arginine, proline, lysine), methane, and a short-chain fatty acid (butanoate), all of which are metabolites widely recognized to be associated with inflammation and metabolic functions. Collectively, our study findings provide key information regarding the biological relevance of microbiome-xenobiotic interactions associated with the ecology of gut microbiota and animal energy metabolism.
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http://dx.doi.org/10.3389/fmicb.2018.02552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207688PMC
October 2018

Transcriptomic and methylomic analysis reveal the toxicological effect of 2,3,7,8-Tetrachlorodibenzodioxin on human embryonic stem cell.

Chemosphere 2018 Sep 10;206:663-673. Epub 2018 May 10.

Partner State Key Laboratory of Environmental and Biological Analysis, Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, China. Electronic address:

Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function. But the effect of dioxin exposure in early stage of fetal development is still largely unknown. In this report, we used the human embryonic stem cell (hESC) line, VAL-3, as a model, together with Methyl-CpG Binding Domain (MBD) protein-enriched genome sequencing and transcriptome sequencing (RNA-seq), in order to determine the dynamic changes of the epigenetic landscape and transcriptional dysregulation in hESC upon dioxin exposure. The bioinformatics analyses including the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis and Ingenuity Pathway Analysis (IPA) highlighted the predisposed neural, hepatic, cardiac and metabolic toxicological effects of dioxin during the fetal development.
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http://dx.doi.org/10.1016/j.chemosphere.2018.05.058DOI Listing
September 2018

Activation of Ca-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells.

Sci Rep 2018 01 18;8(1):1092. Epub 2018 Jan 18.

Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China.

Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms. Cd induced intracellular Ca elevation through phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38 mitogen-activated protein kinases (MAPK) activation and suppressing extracellular signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell death and inhibit cell proliferation. Cd induced p38 activation also contribute to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467 reinstated Cd-induced elevation of intracellular Ca and apoptosis, and it also increased cell proliferation and restored autophagic flux by switching p38 to ERK pathway. The identification of the activation of CaSR-mediated protective pathway in renal cells sheds light on a possible cellular protective mechanism against Cd-induced kidney injury.
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http://dx.doi.org/10.1038/s41598-018-19327-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773512PMC
January 2018

Identification of immune-related genes in gill cells of Japanese eels (Anguilla japonica) in adaptation to water salinity changes.

Fish Shellfish Immunol 2018 Feb 18;73:288-296. Epub 2017 Dec 18.

Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu, 212000, China. Electronic address:

The changes in ambient salinity influence ion and water homeostasis, hormones secretion, and immune response in fish gills. The physiological functions of hormones and ion transporters in the regulation of gill-osmoregulation have been widely studied, however the modulation of immune response under salinity changes is not determined. Using transcriptome sequencing, we obtained a comprehensive profile of osmo-responsive genes in gill cells of Japanese eel (Anguilla japonica). Herein, we applied bioinformatics analysis to identify the immune-related genes that were significantly higher expressed in gill pavement cells (PVCs) and mitochondrial-rich cells (MRCs) in freshwater (FW) than seawater (SW) adapted fish. We validated the data using the real-time qPCR, which showed a high correlation between the RNA-seq and real-time qPCR data. In addition, the immunohistochemistry results confirmed the changes of the expression of selected immune-related genes, including C-reactive protein (CRP) in PVCs, toll-like receptor 2 (TLR2) in MRCs and interleukin-1 receptor type 2 (IL-1R2) in both PVCs and MRCs. Collectively our results demonstrated that those immune-related genes respond to salinity changes, and might trigger related special signaling pathways and network. This study provides new insights into the impacts of ambient salinity changes on adaptive immune response in fish gill cells.
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http://dx.doi.org/10.1016/j.fsi.2017.12.026DOI Listing
February 2018

Transcriptomic and Functional Analyses on the Effects of Dioxin on Insulin Secretion of Pancreatic Islets and β-Cells.

Environ Sci Technol 2017 Oct 21;51(19):11390-11400. Epub 2017 Sep 21.

Croucher Institute for Environmental Sciences, Partner State Key Laboratory of Environmental and Biological Analysis, Department of Biology, Hong Kong Baptist University , Hong Kong SAR, China.

In this study, transcriptomic and Ingenuity Pathway Analysis (IPA) underlined that an ex-vivo TCDD treatment (0.1 nM) stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line (Min-6) validated the stimulatory effects of TCDD (0.1 and 1 nM) on basal-insulin secretion. At 0.1 nM TCDD treatment on Min-6, Western blot analysis showed activation of ERK1/2 and decreased expression of pyruvate dehydrogenase kinase (PDK). A reduction of PDK expression is associated with an increase of pyruvate dehydrogenase flux. This observation was supported by the detection of significantly higher cellular ATP levels, an increase of glucose-stimulated-insulin-secretion (GSIS), and an inhibition of the AMPK pathway. At 1 nM TCDD treatment on Min-6, significant inhibitions of the Akt-mTOR pathway, cellular ATP production, and GSIS were evident. The experimental studies in Min-6 supported the IPA of transcriptomic data in pancreatic islets. Collectively, TCDD treatment caused an elevated basal-insulin release in both islets and β-cell cultures. Moreover, our data revealed that the modulation of the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways might be an important component of the mechanism for the TCDD-perturbing effects on ATP production in β-cells in affecting insulin secretion.
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http://dx.doi.org/10.1021/acs.est.7b02830DOI Listing
October 2017

Effects of in Utero PFOS Exposure on Transcriptome, Lipidome, and Function of Mouse Testis.

Environ Sci Technol 2017 Aug 12;51(15):8782-8794. Epub 2017 Jul 12.

Partner State Key Laboratory of Environmental and Biological Analysis, Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University , Hong Kong.

Transcriptomic and LC-MS/MS-based targeted lipidomic analyses were conducted to identify the effects of in utero PFOS exposure on neonatal testes and its relation to testicular dysfunction in adult offspring. Pregnant mice were orally administered 0.3 and 3 μg PFOS/g body weight until term. Neonatal testes (P1) were collected for the detection of PFOS, and were subjected to omics study. Integrated pathway analyses using DAVID, KEGG, and IPA underlined the effects of PFOS exposure on lipid metabolism, oxidative stress and cell junction signaling in testes. LC-MS/MS analysis showed that the levels of adrenic acid and docosahexaenoic acid (DHA) in testes were significantly reduced in the PFOS treatment groups. A significant linear decreasing trend in eicosapentaenoic acid and DHA with PFOS concentrations was observed. Moreover, LOX-mediated 5-hydroxyeicosatetraenoic acids (HETE) and 15-HETE from arachidonic acid in the testes were significantly elevated and a linear increasing trend of 15-HETE concentrations was detected with doses of PFOS. The perturbations of lipid mediators suggested that PFOS has potential negative impacts on testicular functions. Postnatal analysis of male offspring at P63 showed significant reductions in serum testosterone and epididymal sperm count. This study sheds light into the as yet unrevealed action of PFOS on lipid mediators in affecting testicular functions.
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http://dx.doi.org/10.1021/acs.est.7b02102DOI Listing
August 2017

Transcriptome sequencing reveals prenatal PFOS exposure on liver disorders.

Environ Pollut 2017 Apr 25;223:416-425. Epub 2017 Jan 25.

Croucher Institute for Environmental Sciences, Department of Biology, Partner State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, China. Electronic address:

Perfluorooctane sulfonate (PFOS), a hepatic toxicant and a potential hepatocarcinogen, is commonly used in industrial products. The widespread contamination of PFOS in human maternal and cord blood has raised concerns about its potential risks to the fetus. It is believed that adverse environmental exposure during the critical period of embryo development can have long-lasting consequences in later life. In this report, we used transcriptome sequencing, followed by bioinformatics analysis, to elucidate the potential hepatotoxic and hepatocarcinogenic effects of prenatal PFOS exposure in the fetus. Our results demonstrated that prenatal PFOS exposure could activate the synthesis and metabolism of fatty acids and lipids, leading to liver damage and interference with liver development in the fetus. In addition, a number of cancer-promoting signaling pathways, including Wnt/β-catenin, Rac, and TGF-β, were found to be activated in the fetal liver. More importantly, hepatic transaminase activity, including aspartate aminotransferase and alanine transaminase activity, was induced in the liver of mice offspring after prenatal PFOS exposure. For the first time, our results demonstrate that the hepatotoxic effects of prenatal exposure to PFOS may predispose to a long-term liver disorder in the offspring.
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http://dx.doi.org/10.1016/j.envpol.2017.01.041DOI Listing
April 2017

Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition.

Oncotarget 2017 Apr;8(16):25897-25914

School of Biological Sciences, University of Hong Kong, Hong Kong.

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors.
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http://dx.doi.org/10.18632/oncotarget.13071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432225PMC
April 2017

Bisphenol A alters gut microbiome: Comparative metagenomics analysis.

Environ Pollut 2016 Nov 21;218:923-930. Epub 2016 Aug 21.

Croucher Institute for Environmental Sciences, Partner State Key Laboratory of Environmental and Biological Analysis, Department of Biology, Hong Kong Baptist University, Hong Kong, China. Electronic address:

Mounting evidence has shown that an alteration of the gut microbiota is associated with diet, and plays an important role in animal health and metabolic diseases. However, little is known about the influence of environmental contaminants on the gut microbial community. Bisphenol A (BPA), which is widely used for manufacturing plastic products, has recently been classified as an environmental obesogen. Although many studies have demonstrated the metabolic-disrupting effects of BPA on liver and pancreatic functions, the possible effects of this synthetic compound on the metabolic diversity of the intestinal microbiota is unknown. Using 16S rRNA gene sequencing analysis on caecum samples of CD-1 mice, the present study aimed to test the hypothesis that dietary BPA intake may influence the gut microbiota composition and functions, an important attributing factor to development of the metabolic syndrome. A high-fat diet (HFD) and high-sucrose diet (HSD) were included as the positive controls for comparing the changes in the intestinal microbial profiles. Our results demonstrated a significant reduction of species diversity in the gut microbiota of BPA-fed mice. Alpha and beta diversity analyses showed that dietary BPA intake led to a similar gut microbial community structure as that induced by HFD and HSD in mice. In addition, comparative analysis of the microbial communities revealed that both BPA and a HFD favored the growth of Proteobacteria, a microbial marker of dysbiosis. Consistently, growth induction of the family Helicobacteraceae and reduction of the Firmicutes and Clostridia populations were observed in the mice fed BPA or a HFD. Collectively, our study highlighted that the effects of dietary BPA intake on the shift of microbial community structure were similar to those of a HFD and HSD, and revealed microbial markers for the development of diseases associated with an unstable microbiota.
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http://dx.doi.org/10.1016/j.envpol.2016.08.039DOI Listing
November 2016

Hypoxia causes transgenerational impairments in reproduction of fish.

Nat Commun 2016 07 4;7:12114. Epub 2016 Jul 4.

State Key Laboratory in Marine Pollution, Hong Kong SAR, China.

Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans.
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http://dx.doi.org/10.1038/ncomms12114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932196PMC
July 2016

Fatty liver disease induced by perfluorooctane sulfonate: Novel insight from transcriptome analysis.

Chemosphere 2016 Sep 9;159:166-177. Epub 2016 Jun 9.

Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China. Electronic address:

Perfluorooctane sulfonate (PFOS), a hepato-toxicant and potential non-genotoxic carcinogen, was widely used in industrial and commercial products. Recent studies have revealed the ubiquitous occurrence of PFOS in the environment and in humans worldwide. The widespread contamination of PFOS in human serum raised concerns about its long-term toxic effects and its potential risks to human health. Using fatty liver mutant foie gras (fgr(-/-))/transport protein particle complex 11 (trappc11(-/-)) and PFOS-exposed wild-type zebrafish embryos as the study model, together with RNA sequencing and comparative transcriptomic analysis, we identified 499 and 1414 differential expressed genes (DEGs) in PFOS-exposed wild-type and trappc11 mutant zebrafish, respectively. Also, the gene ontology analysis on common deregulated genes was found to be associated with different metabolic processes such as the carbohydrate metabolic process, glycerol ether metabolic process, mannose biosynthetic process, de novo' (Guanosine diphosphate) GDP-l-fucose biosynthetic process, GDP-mannose metabolic process and galactose metabolic process. Ingenuity Pathway Analysis further highlighted that these deregulated gene clusters are closely related to hepatitis, inflammation, fibrosis and cirrhosis of liver cells, suggesting that PFOS can cause liver pathogenesis and non-alcoholic fatty liver disease in zebrafish. The transcriptomic alterations revealed may serve as biomarkers for the hepatotoxic effect of PFOS.
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http://dx.doi.org/10.1016/j.chemosphere.2016.05.060DOI Listing
September 2016

Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model.

Biochim Biophys Acta 2016 06 10;1862(6):1147-58. Epub 2016 Mar 10.

Department of Biology, Hong Kong Baptist University, Hong Kong. Electronic address:

Treacher Collins Syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects, including the downward slanting palpebral fissures, hypoplasia of the facial bones, and cleft palate (CP). Over 90% of patients with TCS have a mutation in the TCOF1 gene. However, some patients exhibit mutations in two new causative genes, POLR1C and POLR1D, which encode subunits of RNA polymerases I and III, that affect ribosome biogenesis. In this study, we examine the role of POLR1C in TCS using zebrafish as a model system. Our data confirmed that polr1c is highly expressed in the facial region, and dysfunction of this gene by knockdown or knock-out resulted in mis-expression of neural crest cells during early development that leads to TCS phenotype. Next generation sequencing and bioinformatics analysis of the polr1c mutants further demonstrated the up-regulated p53 pathway and predicted skeletal disorders. Lastly, we partially rescued the TCS facial phenotype in the background of p53 mutants, which supported the hypothesis that POLR1C-dependent type 3 TCS is associated with the p53 pathway.
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http://dx.doi.org/10.1016/j.bbadis.2016.03.005DOI Listing
June 2016

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.

Nat Commun 2016 Mar 7;7:10872. Epub 2016 Mar 7.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
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http://dx.doi.org/10.1038/ncomms10872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786676PMC
March 2016

Transcriptomic analysis reveals specific osmoregulatory adaptive responses in gill mitochondria-rich cells and pavement cells of the Japanese eel.

BMC Genomics 2015 Dec 18;16:1072. Epub 2015 Dec 18.

Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Background: Homeostasis of ions and water is important for the maintenance of cellular functions. The regulation of the homeostasis is particularly important in euryhaline fish that migrate between freshwater (FW) and seawater (SW) environments. The fish gill, the major tissue that forms an interface separating the extracellular fluids and external water environment, has an effective transport system to maintain and regulate a constant body osmolality. In fish gills, the two major epithelial cells, pavement cells (PVCs) and mitochondria-rich cells (MRCs), are known to play key and complementary roles in ion transport at the interface. Discovering the robust mechanisms underlying the two cell types' response to osmotic stress would benefit our understanding of the fundamental mechanism allowing PVCs and MRCs to handle osmotic stress. Owing to the limited genomic data available on estuarine species, existing knowledge in this area is slim. In this study, transcriptome analyses were conducted using PVCs and MRCs isolated from Japanese eels adapted to FW or SW environments to provide a genome-wide molecular study to unravel the fundamental processes at work.

Results: The study identified more than 12,000 transcripts in the gill cells. Interestingly, remarkable differential expressed genes (DEGs) were identified in PVCs (970 transcripts) instead of MRCs (400 transcripts) in gills of fish adapted to FW or SW. Since PVCs cover more than 90 % of the gill epithelial surface, the greater change in gene expression patterns in PVCs in response to external osmolality is anticipated. In the integrity pathway analysis, 19 common biological functions were identified in PVCs and MRCs. In the enriched signaling pathways analysis, most pathways differed between PVCs and MRCs; 14 enriched pathways were identified in PVCs and 12 in MRCs. The results suggest that the osmoregulatory responses in PVCs and MRCs are cell-type specific, which supports the complementary functions of the cells in osmoregulation.

Conclusions: This is the first study to provide transcriptomic analysis of PVCs and MRCs in gills of eels adapted to FW or SW environments. It describes the cell-type specific transcriptomic network in different tonicity. The findings consolidate the known osmoregulatory pathways and provide molecular insight in osmoregulation. The presented data will be useful for researchers to select their targets for further studies.
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http://dx.doi.org/10.1186/s12864-015-2271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683740PMC
December 2015

Data for transcriptomic and iTRAQ proteomic analysis of Anguilla japonica gills in response to osmotic stress.

Data Brief 2015 Jun 4;3:120-5. Epub 2015 Mar 4.

Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China ; Croucher Institute for Environmental Sciences, Hong Kong Baptist University, Hong Kong SAR, China.

This article contains data related to the two research articles titled Transcriptomic and iTRAQ proteomic approaches reveal novel short-term hyperosmotic stress responsive proteins in the gill of the Japanese eel (Anguilla japonica) (Tse et al. [1]) and iTRAQ-based quantitative proteomic analysis reveals acute hypo-osmotic responsive proteins in the gills of the Japanese eel (Anguilla japonica) (Tse et al. [2]). The two research articles show the usefulness of combining transcriptomic and proteomic approaches to provide molecular insights of osmoregulation mechanism in a non-model organism, the Japanese eel. The information presented here combines the raw data from the two studies and provides an overview on the physiological functions of fish gills.
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http://dx.doi.org/10.1016/j.dib.2015.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510098PMC
June 2015

Transcriptomic responses of corpuscle of Stannius gland of Japanese eels (Anguilla japonica) to changes in water salinity.

Sci Rep 2015 Apr 24;5:9836. Epub 2015 Apr 24.

Department of Biology, Hong Kong Baptist University, Hong Kong SAR.

Physiological studies of a unique endocrine gland in fish, named corpuscles of Stannius (CS), described a Ca2(+)-regulatory function for this gland mediated by stanniocalcin-1, a hypocalcemic polypeptide hormone. However, to date, the endocrine functions of the glands have not been completely elucidated.We hypothesized that other unidentified active principles in the glands are involved in the regulation of plasma ion (Na(+), Ca2(+)) and/or blood pressure. In this study, transcriptome sequencing of CS glands was performed using Japanese eels (Anguilla japonica) adapted to freshwater (FW) or seawater (SW) to reveal the presence and differential expression of genes encoding proteins related to the ion-osmoregulatory and pressor functions. We acquired a total of 14.1 Mb and 12.1 Mb quality-trimmed reads from the CS glands collected from FW and SW adapted eels, respectively. The de novo assembly resulted in 9254 annotated genes. Among them, 475 genes were differentially expressed with 357 up- and 118 down-regulated in the SW group. Gene ontology analysis further demonstrated the presence of natriuresis and pressor related genes. In summary, ours is the first study using high-throughput sequencing to identify gene targets that could explain the physiological importance of the CS glands.
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http://dx.doi.org/10.1038/srep09836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386212PMC
April 2015

Tissue-specific transcriptome assemblies of the marine medaka Oryzias melastigma and comparative analysis with the freshwater medaka Oryzias latipes.

BMC Genomics 2015 Feb 27;16:135. Epub 2015 Feb 27.

School of Biological Sciences, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China.

Background: The marine medaka Oryzias melastigma has been demonstrated as a novel model for marine ecotoxicological studies. However, the lack of genome and transcriptome reference has largely restricted the use of O. melastigma in the assessment of in vivo molecular responses to environmental stresses and the analysis of biological toxicity in the marine environment. Although O. melastigma is believed to be phylogenetically closely related to Oryzias latipes, the divergence between these two species is still largely unknown. Using Illumina high-throughput RNA sequencing followed by de novo assembly and comprehensive gene annotation, we provided transcriptomic resources for the brain, liver, ovary and testis of O. melastigma. We also investigated the possible extent of divergence between O. melastigma and O. latipes at the transcriptome level.

Results: More than 14,000 transcripts across brain, liver, ovary and testis in marine medaka were annotated, of which 5880 transcripts were orthologous between O. melastigma and O. latipes. Tissue-enriched genes were identified in O. melastigma, and Gene Ontology analysis demonstrated the functional specificity of the annotated genes in respective tissue. Lastly, the identification of marine medaka-enriched transcripts suggested the necessity of generating transcriptome dataset of O. melastigma.

Conclusions: Orthologous transcripts between O. melastigma and O. latipes, tissue-enriched genes and O. melastigma-enriched transcripts were identified. Genome-wide expression studies of marine medaka require an assembled transcriptome, and this sequencing effort has generated a valuable resource of coding DNA for a non-model species. This transcriptome resource will aid future studies assessing in vivo molecular responses to environmental stresses and those analyzing biological toxicity in the marine environment.
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http://dx.doi.org/10.1186/s12864-015-1325-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352242PMC
February 2015

Methionine oxidation in albumin by fine haze particulate matter: an in vitro and in vivo study.

J Hazard Mater 2014 Jun 21;274:384-91. Epub 2014 Apr 21.

School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address:

The potential effects of inhaled fine particulate matter (PM2.5), found in haze episodes, on the oxidation of the proteins in the lungs are not well understood. We investigated the effects of PM2.5 from haze episodes on protein oxidation. PM2.5 was collected from the air pollution in Beijing (BJ), Xian (XA), Xiamen (XM) and Hong Kong (HK) during a period of intensive haze episodes. The chemical characteristics of these samples and their effects on albumin oxidation were investigated. The levels of PM2.5 in BJ and XA were 4-6 times higher than in XM and HK. The concentrations of the polycyclic aromatic hydrocarbons (PAHs) components of the PM2.5 from BJ and XA were 10 times higher than those found in XM and HK. The haze PM2.5 increased oxidative stress. Addition of PM2.5 samples collected from haze episodes to albumin in vitro resulted in oxidation of methionine moieties; nasal instillation of PM2.5 suspensions in mice resulted in oxidation of methionine in the albumin in the bronchoalveolar lavage fluid. The methionine moieties participate in peptide chain crosslinking, and methionine oxidation in the albumin could be attributed to the PAH compounds. Our findings may be helpful in explaining the potential respiratory effects during haze episodes.
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http://dx.doi.org/10.1016/j.jhazmat.2014.04.029DOI Listing
June 2014

iTRAQ-based quantitative proteomic analysis reveals acute hypo-osmotic responsive proteins in the gills of the Japanese eel (Anguilla japonica).

J Proteomics 2014 Jun 3;105:133-43. Epub 2014 Feb 3.

Department of Biology, Hong Kong Baptist University, Hong Kong; Croucher Institute for Environmental Sciences, Hong Kong Baptist University, Hong Kong. Electronic address:

Unlabelled: Osmoregulation in fish has been a classical research topic for several decades. Salmon and eels are the widely used model animals because of their wide distribution in different geographical locations and spawning migration between fresh- and salt-water habitats. Numerous fish osmoregulatory hormones and ion transporters were identified for their essential roles in acclimation and adaptation to waters of different salinities. Because of the lack of a genomic database, the scope of most studies, however, is very limited. Recently, our group reported the first high-throughput transcriptomic and proteomic studies to identify hyperosmotic-responsive genes/proteins in gills of Japanese eels. In this study, we aimed to decipher changes in hypo-osmotic-responsive proteins in fish acclimating from seawater (SW) to freshwater (FW) conditions. We collected gill samples from SW-adapted and SW-to-FW-acclimating fish. The respective gill proteins were extracted and labeled using isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed using a high-resolution mass spectrometer. In the short-term transfer from SW to FW, 51 hypo-responsive proteins were detected, and 24 unique hypo-osmotic-responsive proteins were identified (15 up-regulated and nine down-regulated proteins). Our data support the use of an omics approach to facilitate the application of functional genomics in non-model organisms.

Biological Significance: By combining transcriptomic and proteomic approaches, the study has provided the most comprehensive, targeted investigation of eel gill hypo-osmotic responsive proteins that provides molecular insights of osmoregulation mechanisms in a non-model organism, eel. This article is part of a Special Issue entitled: Proteomics of non-model organisms.
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http://dx.doi.org/10.1016/j.jprot.2014.01.025DOI Listing
June 2014

Understanding the regulation of estivation in a freshwater snail through iTRAQ-based comparative proteomics.

J Proteome Res 2013 Nov 2;12(11):5271-80. Epub 2013 Oct 2.

Department of Biology, Hong Kong Baptist University , Hong Kong, China.

The apple snail Pomacea canaliculata is a freshwater gastropod with a remarkable ability to withstand seasonal or unpredictable dry conditions by entering estivation. Studies of P. canaliculata using conventional biochemical and the individual gene approaches have revealed the expressional changes of several enzymes and antioxidative genes in response to estivation and arousal. In this study, we applied iTRAQ-coupled two-dimensional LC-MS/MS to identify and quantify the global protein expression during the estivation and arousal of P. canaliculata. A total of 1040 proteins were identified, among which 701 proteins were quantified and compared across four treatments (i.e., control, active snails; short-term estivation, 3 days of exposure to air; prolonged estivation, 30 days of exposure to air; and arousal, 6 h after resubmergence in water) revealing 53 differentially expressed proteins. A comparison of protein expression profiles across treatments indicated that the proteome of this species was very insensitive to initial estivation, with only 9 proteins differentially expressed as compared with the control. Among the 9 proteins, the up-regulations of two immune related proteins indicated the initial immune response to the detection of stress cues. Prolonged estivation resulted in many more differentially expressed proteins (47 compared with short-term estivation treatment), among which 16 were down-regulated and 31 were up-regulated. These differentially expressed proteins have provided the first global picture of a shift in energy usage from glucose to lipid, prevention of protein degradation and elevation of oxidative defense, and production of purine for uric acid production to remove toxic ammonia during prolonged estivation in a freshwater snail. From prolonged estivation to arousal, only 6 proteins changed their expression level, indicating that access to water and food alone is not a necessary condition to reactivate whole-sale protein expression. A comparison with hibernation and diapause revealed many similar molecular mechanisms of hypometabolic regulation across the animal kingdom.
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http://dx.doi.org/10.1021/pr400570aDOI Listing
November 2013
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