Publications by authors named "Jingzeng Cai"

31 Publications

Melatonin ameliorates trimethyltin chloride-induced cardiotoxicity: The role of nuclear xenobiotic metabolism and Keap1-Nrf2/ARE axis-mediated pyroptosis.

Biofactors 2021 Sep 27. Epub 2021 Sep 27.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, P.R. China.

Trimethyltin chloride (TMT) is a stabilizer for polyvinyl chloride plastics that causes serious health hazards in nontarget organisms. Melatonin (MT) exhibits powerful protective effects in cardiac diseases. As a new environmental pollutant, TMT-induced cardiotoxicity and the protective effects of MT remain unclear. To explore this, the mice were treated with TMT (2.8 mg/kg) and/or MT (10 mg/kg) for 7 days. Firstly, the histopathological and ultrastructural evaluation showed that TMT induced cardiac damage, tumescent rupture and nuclear pyknosis. Moreover, TMT elevated the expressions of pyroptosis genes NLRP3, ASC and Cas1 and inflammation factors IL-6, IL-17 and TNFα. Secondly, TMT reduced antioxidant enzymes (GSH, CAT and T-AOC) via decreasing the expression of genes associated with the Keap1-Nrf2/ARE pathway to increase oxidative stress. Thirdly, TMT decreased the expression of genes associated with the ARE-driven drug metabolizing enzymes (DMEs), including Akr7a3, Akr1b8, and Akr1b10. Besides, TMT upregulated the mRNA expression of nuclear Xenobiotic metabolism on cytochrome P450s enzymes via increasing the expression of CAR, PXP, and AHR genes. Furthermore, MT treatment mitigated the aforementioned adverse changes induced by TMT. Overall, these results demonstrated that TMT caused pyroptosis and inflammation to aggravate cardiac damage via inducing excessive oxidative stress, imbalance of DMEs homeostasis, and nuclear Xenobiotic metabolism disorder, which could be alleviated by MT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/biof.1787DOI Listing
September 2021

Cadmium exposure triggers oxidative stress, necroptosis, Th1/Th2 imbalance and promotes inflammation through the TNF-α/NF-κB pathway in swine small intestine.

J Hazard Mater 2021 Jul 20;421:126704. Epub 2021 Jul 20.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. Electronic address:

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1β, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126704DOI Listing
July 2021

Selenium deficiency causes apoptosis through endoplasmic reticulum stress in swine small intestine.

Biofactors 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Selenium (Se) plays a crucial role in intestinal health. However, the specific mechanism by which deficiency of Se causes intestinal damage remains unclear. This study was to explore whether Se deficiency can cause ER stress and induce apoptosis in swine small intestine. We established the Se deficiency swine model in vivo and the intestinal epithelial (IPEC-J2) cell Se deficiency model in vitro. The results of morphological observation showed that Se deficiency caused structural damage in intestinal villi and the decrease of goblet cell structure. The apoptotic characteristics such as nucleolar condensation, mitochondrial swelling, and apoptotic bodies were observed in the IPEC-J2 cells. The results of acridine orange/ethidium bromide and mitochondrial membrane potential fluorescence staining in vitro showed that there were more apoptotic cells in the Se-deficiency group than that in the control group. The protein and/or mRNA expression levels of Bax, Bcl-2, caspase 3, caspase 8, caspase 9, cytc, PERK, ATF6, IRE, XBP1, CHOP, GRP78, which are related to ER stress-apoptosis pathway, were significantly increased in the Se-deficient group which compared with the control group in vivo and in vitro were consistent. These results indicated that Se deficiency induced ER stress and increased the apoptosis in swine small intestine and IPEC-J2 cells and then caused the damage in swine small intestinal tissue. Besides, the results of gene expressions in our experiment proved that ER stress induced by Se deficiency promoted apoptosis. These results filled the blank in the mechanism of Se deficiency-induced intestinal injury in swine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/biof.1762DOI Listing
June 2021

NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1β/IkB-α-NF-κB-NLRP3 feedback loop in swine.

Toxicology 2021 04 13;453:152720. Epub 2021 Feb 13.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China. Electronic address:

Cadmium (Cd) chloride, as widely distributed toxic environmental pollutants by using in industry, severely imperils animal and human health. Pyroptosis is a Cas1-dependent pro-inflammatory programmed cell death and involves in various types of diseases. Nevertheless, the mechanism of pyroptosis and Cd-induced neurotoxicity remains obscure. To investigate the specific molecular mechanisms of Cd-induced neurotoxicity, 10 weaned piglets were randomly divided into 2 groups treated with 0 and 20 mg/kg CdCl in the diet for 40 days. The levels of pyroptosis, mitochondrial and inflammation-related genes were validated by qRT-PCR and WB in vivo. Our results revealed that Cd caused cerebral histopathology lesions, inducing cerebral pyroptosis and the mass generation of inflammatory cytokines, as indicated by the increased NLRP3 inflammasome activation (NLRP3, Cas1 and ASC) and the upregulation of inflammation factors IL-2, IL-6, IL-7 and inhibition of IL-10. Subsequently, further research indicated that Cd triggered pyroptosis via activating the TRAF6-IkB-α-NF-κB pathway, which interfered with the phosphorylation and ubiquitination of IkB-α. Furthermore, Cd caused mitochondrial dysfunction and fragmentation by inhibiting the AMPK-PGC-1α-NRF1/2 signaling pathway and reduced the expression of mitochondrial-related regulatory factors OPA1, TFAM and mtDNA, resulting in the increase of NLRP3 inflammasome. Besides, we found eight hub genes (IKK, IKB-α, NLRP3, TRAF6, NF-κB, AMPK, TNFα and PGC-1α), mainly related to the interaction between the NF-κB pathway and NLRP3 inflammasome. Overall, these results demonstrated that Cd could promote the IL-1β/IkB-α-NF-κB-NLRP3 inflammasome activation positive feedback loop to result in neuroinflammation in swine, which provided new insights in understanding Cd-induced toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2021.152720DOI Listing
April 2021

Selenoprotein Gpx3 knockdown induces myocardial damage through Ca leaks in chickens.

Metallomics 2020 11 24;12(11):1713-1728. Epub 2020 Sep 24.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.

Glutathione peroxidase 3 (Gpx3) is a pivotal selenoprotein that acts as an antioxidant. However, the role of Gpx3 in maintaining the normal metabolism of cardiomyocytes remains to be elucidated in more detail. Herein, we employed a model of Gpx3 interference in chicken embryos in vivo and Gpx3 knockdown chicken cardiomyocytes in vitro. Real-time PCR, western blotting and fluorescent staining were performed to detect reactive oxygen species (ROS), the calcium (Ca) concentration, endoplasmic reticulum (ER) stress, myocardial contraction, inflammation and heat shock proteins (HSPs). Our results revealed that Gpx3 suppression increased the level of ROS, which induced Ca leakage in the cytoplasm by blocking the expression of Ca channels. The imbalance of Ca homeostasis triggered ER stress and blocked myocardial contraction. Furthermore, we found that Ca imbalance in the cytoplasm induced severe inflammation, and HSPs might play a protective role throughout these processes. In conclusion, Gpx3 suppression induces myocardial damage through the activation of Ca-dependent ER stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0mt00027bDOI Listing
November 2020

LncRNA 0003250 accelerates heart autophagy and binds to miR-17-5p as a competitive endogenous RNA in chicken induced by selenium deficiency.

J Cell Physiol 2021 01 15;236(1):157-177. Epub 2020 Jun 15.

Clinical Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Long noncoding RNAs (LncRNAs) have been demonstrated to be associated with a variety of myocardial diseases, but how LncRNAs regulate autophagy in selenium (Se)-deficient myocardial injury is infrequently reported. Here, we screened out a novel long noncoding RNA, microRNA, and ATG7 through transcriptomic results. We employed a Se-deficient chicken model in vivo, and primary cultured cardiomyocytes treated by correlation in vitro. The results showed that Se deficiency upregulated the expression of ATG7, and miR-17-5p inhibited cardiomyocyte autophagy by targeting ATG7. Furthermore, we found that LncRNA 0003250 regulated miR-17-5p, and thus affected the expression of ATG7 and autophagic cell death. Our present study proposed a novel model for the regulation of cardiomyocytes autophagy, which includes LncRNA 0003250, miR-17-5p and ATG7 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se-deficient cardiomyocyte injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.29831DOI Listing
January 2021

Chlorpyrifos induces apoptosis and autophagy in common carp lymphocytes by influencing the TCR γ-dependent PI3K/AKT/JNK pathway.

Fish Shellfish Immunol 2020 Apr 26;99:587-593. Epub 2020 Feb 26.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Chlorpyrifos is an insecticide that is widely used in agricultural production. However, little is known about how chlorpyrifos disrupts lymphocyte homeostasis in common carp. Herein, we identified TCRγ through the results of transcriptome analysis. Subsequently, we established TCR γ knockdown and overexpression models in carp head kidney lymphocyte respectively using RNA interference and the pcDNA3.1 plasmid, respectively. Real-time PCR, fluorescent staining, ultrastructure observation and flow cytometry were used to detect the levels of the PI3K/AKT pathway, autophagy and apoptosis. Our results demonstrated that chlorpyrifos significantly decreased the expression of TCR γ, TCR γ suppression thereby induced increased mRNA expression of TNF-α, Bax, caspase-3, caspase-8, caspase-9 and significantly inhibited the expression of Bcl-2, which indicated that apoptosis was triggered. This conclusion was supported by our flow cytometry and ultrastructure observation results. In addition, the control and TCR γ overexpression groups had normal cell morphology. Moreover, TCR γ suppression activated the expression of Becline-1, ATG5, ATG10, ATG12, ATG16 and reduced the expression of mTOR, with the opposite results observed in the TCR γ overexpression group. Together, these results suggested that TCR γ imbalance triggers apoptosis and autophagy in lymphocyte. Moreover, we found that TCR γ knockdown significantly increased the mRNA expression of JNK and decreased the expression of PI3K and AKT, which indicated that the PI3K/AKT/JNK pathway was activated. Our results reported here indicated that chlorpyrifos induces apoptosis and autophagy in head kidney lymphocyte through the inhibition of TCR γ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2020.02.039DOI Listing
April 2020

Chlorpyrifos induces redox imbalance-dependent inflammation in common carp lymphocyte through dysfunction of T-cell receptor γ.

J Fish Dis 2020 Apr 11;43(4):423-430. Epub 2020 Feb 11.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Chlorpyrifos is a poisonous pesticide that is highly toxic to fish and aquatic organisms. However, there are fewer reports about how chlorpyrifos influences the redox balance of immune cells. Herein, the head kidney tissue treated with chlorpyrifos to do transcriptome analysis and TCR γ was screened out. Subsequently, we established TCR γ knockdown and overexpression carp head kidney lymphocyte models, respectively, by using RNA interference and pcDNA3.1. Real-time PCR, fluorescent staining, oxidation and antioxidant kit were used to detect the related factors. We found that TCR γ knockdown significantly increased the mRNA expression of HSP70 and HSP90 and decreased the mRNA expression of SOD and CAT. Meanwhile, TCR γ knockdown reduced the activities of GSH, GSG-PX, T-AOC, CAT and SOD and increased the content of MDA and H O and activities of iNOS. Adverse results were obtained in TCR γ overexpression group. Additionally, TCR γ knockdown significantly increased the mRNA expression of IFN-γ, IL-1β, IL-8, IL-10, Nrf2 and NF-κB, but relieved TCR γ overexpression, in which the process of inflammation was activated. Our results reported here indicated that chlorpyrifos induces redox imbalance-dependent inflammation in common carp lymphocyte through dysfunction of T-cell receptor γ, and HSPs play potential protective role in entire process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jfd.13138DOI Listing
April 2020

Dysfunction of thioredoxin triggers inflammation through activation of autophagy in chicken cardiomyocytes.

Biofactors 2020 Jul 7;46(4):579-590. Epub 2020 Feb 7.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, People's Republic of China.

Thioredoxin (Txn) is a hydrogen carrier protein and exists widely in organism. Txn deficiency implicates cardiomyocytes injury has been proven. However, the exact mechanism remains unclear. To understand the mechanistic response of cardiomyocytes subsequent to Txn suppression, we established the model of Txn dysfunction by employing gene interference technology (siRNA) and Txn inhibitor (PX-12) in cardiomyocytes. We detected the ROS levels, inflammation factors, and key proteins in the autophagy and apoptosis. In addition, heat map was used for further analysis. Our results revealed that Txn dysfunction increased the release of ROS and induced activation of autophagy via upregulation of Becline-1, LC3-1, 2, which further regulated the inflammatory response, meanwhile, Txn silence inhibited apoptosis in chicken cardiomyocytes through Caspase-3 inhibition. Altogether we concluded that Txn-deficient chicken cardiomyocytes experienced autophagy, which caused severe inflammatory reactions and resulting in damage to cardiomyocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/biof.1625DOI Listing
July 2020

MicroRNA profiling identifies biomarkers in head kidneys of common carp exposed to cadmium.

Chemosphere 2020 May 11;247:125901. Epub 2020 Jan 11.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Cadmium (Cd) is an increasingly important environmental pollutant due to its high toxicity to fish and aquatic animals. In the present study, we cultured common carp (Cyprinus carpio L.) in two groups, a control group and a Cd group, with the Cd group being exposed to Cd for 30 d. The antioxidant enzyme activities of T-AOC and CAT and the GSH content were differentially decreased during Cd exposure. miRNAome profiling indicated that 23 differentially expressed miRNAs were potential biomarkers for Cd exposure; 7 miRNAs were up-regulated, and 16 miRNAs were down-regulated. The expression levels of miR-122, novel-miR6, miR-193a-3p and miR-27a-5p in the Cd group were 0.43-fold, 0.47-fold, 0.49-fold and 2.4-fold greater than in the control group, respectively. qRT-PCR further detected that the expression levels of apoptosis-related genes, including BAX, BAD, BAK, CASPASE9 and PIDD, were differentially increased, while BCL2 was decreased. Western blot analysis showed that the protein expression levels of BAX and BAD were increased and that of BCL2 was differentially decreased during Cd exposure. Alterations in the levels of miR-122, novel-miR6, miR-193a-3p and miR-27a-5p expression may play an important role in diagnosing oxidative stress-induced apoptosis during Cd exposure in the head kidney. These markers may contribute to diagnosing the early stage of Cd exposure in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.125901DOI Listing
May 2020

IGF1 Knockdown Hinders Myocardial Development through Energy Metabolism Dysfunction Caused by ROS-Dependent FOXO Activation in the Chicken Heart.

Oxid Med Cell Longev 2019 24;2019:7838754. Epub 2019 Dec 24.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

Insulin-like growth factor 1 (IGF1) is a multifunctional cellular regulatory factor that can regulate cell growth and development by mediating growth hormone stimulation. However, the mechanism of IGF1 dysfunction in cardiomyocyte development is seldom reported. To study this, we employed the models of IGF1 knockdown in chicken embryo in vivo and in cardiomyocytes in vitro. We detected the antioxidant capacity, PI3K/Akt pathway, energy metabolism-related genes, and myocardial development-related genes. Our results revealed that the low expression of IGF1 can significantly suppress the antioxidant capacity and increase the ROS ( < 0.05) levels, activating the AMPK and PI3K pathway by inhibiting the expression of IRS1. We also found that myocardial energy metabolism is blocked through IGF1, GLUT, and IGFBP inhibition, further inducing myocardial developmental disorder by inhibiting Mesp1, GATA, Nkx2.5, and MyoD expression. Altogether, we conclude that low IGF1 expression can hinder myocardial development through the dysfunction of energy metabolism caused by ROS-dependent FOXO activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/7838754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948330PMC
June 2020

Di-(2-ethyl hexyl) phthalate induces necroptosis in chicken cardiomyocytes by triggering calcium overload.

J Hazard Mater 2020 04 15;387:121696. Epub 2019 Nov 15.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China. Electronic address:

Di-(2-ethyl hexyl)phthalate (DEHP) is a kind of plasticizer that can cause cardiovascular disorders in animals, but its specific mechanism of action has not been determined. We aimed to investigate whether taxifolin (TAX) can antagonize the cytotoxicity of DEHP on cardiomyocytes. Chicken cardiomyocytes were treated with DEHP (500 μM) and/or TAX (0.5 μM) for 24 h. Ca staining showed that the concentration of Ca in the cytoplasm of cardiomyocytes was significantly increased under DEHP stimulation. However, in the DEHP + TAX group, the Ca concentration was largely restored. In addition, the results of necroptosis--fluorescent and flow cytometry analysis showed that the DEHP group had severe necroptosis compared with the control group. The necrotic rate in the DEHP + TAX group was significantly lower than that in the DEHP group. At the mRNA and protein levels, the expression of the necrotic-calcium pathway genes RIPK1, RIPK3, MLKL, FAS, Caspase-8, CAMKII, and SERCA in the DEHP group increased to varying degrees relative to the control group. However, TAX improved this injury. Compared with the DEHP group, the expression of these genes was significantly decreased in the DEHP + TAX group. The present study indicate that DEHP could trigger cardiomyocyte necroptosis through Ca overload, which could be alleviated by TAX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2019.121696DOI Listing
April 2020

DEHP induces immunosuppression through disturbing inflammatory factors and CYPs system homeostasis in common carp neutrophils.

Fish Shellfish Immunol 2020 Jan 30;96:26-31. Epub 2019 Nov 30.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China. Electronic address:

Di-(2-ethylhexyl) phthalate (DEHP), a common pollutant in the water environment, has been reported to be associated with immune functions, especially aquatic organisms. However, whether DEHP exposure causes neutrophils toxicity in common carp is still unclear. To investigate the toxic effect of DEHP on immune functions, common carp neutrophils were exposed to DEHP (40 μmol/L and 200 μmol/L) for 2 h. The common carp neutrophils exposed to DEHP showed a decrease in neutrophil phagocytosis rate compared with control group. DEHP exposure induced a significant decrease in mRNA expression levels of inflammatory cytokines-related genes (Interleukin-6, Interleukin-8, transforming growth factor, tumor necrosis factor (TNF)-α, TNF-R1, TNF-T1, Interferon (IFN)-2a, IFN-g2b, IFN-g1) in common carp neutrophils, while the expression levels of IL-1β and IL-10 were increased compared with control group (P < 0.05). Furthermore, the detection of cytochrome P450 enzyme related genes showed that the mRNA expression levels of CYP (cytochrome P450 proteins)-1A, CYP-1B1, CYP-C1, CYP-2K were significantly decreased, and the mRNA expression level of CYP-3A was significantly reduced (P < 0.05). The results indicated that DEHP could affect the phagocytic ability of neutrophils by regulating the expression of inflammatory cytokines and disrupting cytochrome P450 homeostasis, which caused the immunosuppression in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2019.11.073DOI Listing
January 2020

Taxifolin ameliorates DEHP-induced cardiomyocyte hypertrophy via attenuating mitochondrial dysfunction and glycometabolism disorder in chicken.

Environ Pollut 2019 Dec 11;255(Pt 1):113155. Epub 2019 Sep 11.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China; State Key Laboratory of Animal Nutrition, Beijing 100193, PR China. Electronic address:

Di-(2-ethylhexyl) phthalate (DEHP) is a prevalent environmental contaminant that severely impacts the health of human and animals. Taxifolin (TAX), a plant flavonoid isolated from yew, exerts protective effects on cardiac diseases. Nevertheless, whether DEHP could induce cardiomyocyte hypertrophy and its mechanism remains unclear. This study aimed to highlight the specific molecular mechanisms of DEHP-induced cardiomyocyte hypertrophy and the protective potential of TAX against it. Chicken primary cardiomyocytes were treated with DEHP (500 μM) and/or TAX (0.5 μM) for 24 h. The levels of glucose and adenosine triphosphate (ATP) were detected, and cardiac hypertrophy-related genes were validated by real-time quantitative PCR (qRT-PCR) and Western blot (WB) in vitro. The results showed that DEHP-induced cardiac hypertrophy was ameliorated by TAX, as indicated by the increased cardiomyocyte area and expression of atrial natriuretic peptide (ANP), natriuretic peptides A-like (BNP) and β-myosin heavy cardiac muscle (β-MHC). Furthermore, DEHP induced cardiac hypertrophy via the interleukin 6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in vitro. In addition, DEHP disrupted mitochondrial function and glycometabolism by activating the insulin-like growth factor 1 (IGF1)/phosphatidylinositol 3-kinase (PI3K) pathway and the peroxisome proliferator activated receptors (PPARs)/PPARG coactivator 1 alpha (PGC-1α) pathway to induce cardiac hypertrophy in vitro. Intriguingly, those DEHP-induced changes were obviously alleviated by TAX treatment. Taken together, cardiac hypertrophy was induced by DEHP via activating the IL-6/JAK/STAT3 signaling pathway, triggering glycometabolism disorder and mitochondrial dysfunction in vitro, can be ameliorated by TAX. Our findings may provide a feasible molecular mechanism for the treatment of cardiomyocyte hypertrophy induced by DEHP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2019.113155DOI Listing
December 2019

lnc-3215 Suppression Leads to Calcium Overload in Selenium Deficiency-Induced Chicken Heart Lesion via the lnc-3215-miR-1594-TNN2 Pathway.

Mol Ther Nucleic Acids 2019 Dec 12;18:1-15. Epub 2019 Aug 12.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. Electronic address:

Selenium deficiency has been proven to induce calcium disorders in the chicken heart. However, detailed regulatory mechanisms, e.g., the long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory axis, have not yet been described. Here, we point out lnc-2315, miR-1594, and Troponin T (TNNT2) based on the results of lncRNA and miRNA comparative genomics group analysis of Se-deficient chicken hearts compared with control hearts. We employed lnc-3215 and TNNT2 knockdown, miR-1594 knockdown, and overexpression models in the chicken embryos in vivo, and lnc-3215, miR-1594, and TNNT2 knockdown and overexpression models in cardiomyocytes in vitro. The dual-luciferase reporter assay and quantitative real-time PCR were used to confirm the relationships between miR-1594 and TNNT2, lnc-3215, and miR-1594 in cardiomyocytes. Our results revealed that TNNT2 suppression induced cardiac calcium overload in vivo and in vitro. miR-1594 activates cardiac calcium overload by targeting TNNT2. Moreover, we found that lnc-3215 regulates miR-1594, and thus influences the TNNT2 expression in vivo and in vitro; these conclusions were verified by gene knockdown in chicken embryos. Our present study revealed a novel regulatory model of a calcium program, which comprises lnc-3215, miR-1594, and TNNT2 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se-deficient cardiomyocytes injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2019.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726916PMC
December 2019

Role of miR-731 and miR-2188-3p in mediating chlorpyrifos induced head kidney injury in common carp via targeting TLR and apoptosis pathways.

Aquat Toxicol 2019 Oct 27;215:105286. Epub 2019 Aug 27.

Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Chlorpyrifos (CPF) is an environmental pollutant with increasing importance due to its high toxicity to fish and aquatic animals. In the present study, we divided 120 common carp (Cyprinus carpio L.) into two groups including control group and CPF group, CPF group was exposed to 14.5 μg/L CPF for 30 d. 17 miRNAs were differentially expressed in CPF group head kidney tissues according to the results of miRNAome analysis. In addition, histopathological examination and electron microscopy proved that CPF exposure could lead to damage of head kidney and obvious apoptosis characteristics. The possible target genes of miRNA were predicted using online target gene prediction websites, miRNAome sequencing, GO and KEGG enrichment. miRNAome results showed that expression of miR-731 and miR-2188-3p in CPF group was 0.48 time and 0.45 time as control group, respectively. qRT-PCR results proved the reality of miRNAome. During CPF exposure, mRNA expression of TLR pathway genes and its downstream genes involved in autophagy and apoptosis pathway including TLR1, TLR2, TLR7, TLR9, MyD88, IRAK1, IRAK4, IRF7, PI3K, AKT, mTOR, Caspase3, Caspase8 and Bax were differentially increased under CPF exposure, along with ATG13 and Bcl2 decreased at the same time. Western blot results indicated that apoptosis related protein Caspase3 and Caspase8 were differentially up-regulated in the CPF group. In summary, CPF exposure could induce apoptosis while inhibited autophagy in head kidney of common carp via the regulation of miR-2188-3p and miR-731 by targeting TLR pathway. These results provide new insights for unveiling the biological effects of CPF and miRNAs in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2019.105286DOI Listing
October 2019

Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes.

Ecotoxicol Environ Saf 2019 Nov 20;183:109582. Epub 2019 Aug 20.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, China. Electronic address:

Di-2-ethylhexyl phthalate (DEHP), widely used as a plasticizer, is a ubiquitous artificial pollutant. DEHP can induce biological toxicity in various organs, with an especially high potential for toxicity to the cardiovascular system. Taxifolin (TAX) is used in the treatment of cardiovascular diseases due to its antioxidative capacities. However, it is not clear whether TAX can alleviate apoptosis induced by DEHP exposure through the cytochrome P450 (CYP) pathway in cardiomyocytes. To understand the role of TAX in attenuating cardiomyocyte toxicity induced by DEHP, primary cardiomyocytes were divided into 4 groups (control group, DEHP group, TAX group and DEHP + TAX group). The results showed that in the cardiomyocytes, DEHP initiated apoptosis by increasing the expression of caspase-3, caspase-9, cyt c, and Bax at both the mRNA and protein levels and by decreasing the Bcl-2 levels compared with that of the control group. In addition, the activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidative capacity (T-AOC) were clearly decreased (P < 0.05), while in the DEHP group, the malondialdehyde (MDA) and hydrogen peroxide (HO) levels were observably increased (P < 0.05), compared with those in control group. Furthermore, compared with the control group, the DEHP group demonstrated a clear partial decrease in the expression of the mRNA levels of CYP1B1 and CYP2C18 (P < 0.05), and DEHP/TAX cotreatment partially prevented apoptosis and oxidative stress damage (P < 0.05). These results showed that exposure to DEHP induced apoptosis in chicken cardiomyocytes, while TAX could antagonize the toxicity of DEHP on cardiomyocytes by attenuating oxidative stress responses and modulating CYPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.109582DOI Listing
November 2019

Impact of Selenium Deficiency on Inflammation, Oxidative Stress, and Phagocytosis in Mouse Macrophages.

Biol Trace Elem Res 2020 Mar 19;194(1):237-243. Epub 2019 Jun 19.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Although it has been reported that selenium (Se) deficiency can trigger inflammation, however, there are few reports on the effect of Se on the function of mouse peritoneal macrophages. Herein, we examined the expression of inflammatory factors, oxidative stress levels, and phagocytosis for primary-cultured peritoneal macrophages using control and Se-deficient groups. Our results revealed that Se deficiency induced the accumulation of oxygen free radicals and weakened antioxidant capacity. Se deficiency also significantly increased the expression of inflammation factors including iNOS, IL-1β, IL-12, IL-10, PTGe, and NF-κB. Meanwhile, Se suppression restrained macrophage production of TNF-α. The results of the phagocytosis assay demonstrated that Se deficiency inhibited the phagocytosis of macrophages. In conclusion, Se-deficient macrophages undergo severe inflammation through the NF-κB pathway due to the accumulation of oxygen free radicals and are hindered in their phagocytic capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-019-01775-7DOI Listing
March 2020

Mir-215-5p induces autophagy by targeting PI3K and activating ROS-mediated MAPK pathways in cardiomyocytes of chicken.

J Inorg Biochem 2019 04 18;193:60-69. Epub 2019 Jan 18.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China. Electronic address:

Our previous study revealed that selenium (Se) deficiency can cause myocardial injury through triggering autophagy. MicroRNAs (miRNAs) play crucial roles in autophagic cell death. However, the relationship between miRNAs and myocardial autophagy injury caused by Se deficiency remains unclear. We selected differential microRNA-215-5p (miR-215-5p) in Se-deficient myocardial tissue using high-throughput miRNA-sequencing. To further explore the role of miR-215-5p in myocardial injury, overexpression/knockdown of miR-215-5p in primary cardiomyocyte model was established by miRNAs interference technology. In this study, we report that miR-215-5p can promote myocardial autophagy by directly binding to the 3'untranslated region (3'UTR) of phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K). Its target gene PI3K was confirmed by dual luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in cardiomyocytes. Our results showed that overexpression of miR-215-5p could trigger myocardial autophagy through PI3K-threonine-protein kinase (AKT)-target of rapamycin (TOR) pathway. Further studies revealed that autophagic cell death was dependent on the activation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 kinase (p38) and generation of reactive oxygen species (ROS) in overexpression of miR-215-5p in cardiomyocytes. On the contrary, miR-215-5p inhibitor can enhance cell survival capacity against autophagy by inhibiting ROS-mitogen-activated protein kinase (MAPK) pathways and activating the PI3K/AKT/TOR pathway in cardiomyocytes. Together, our findings support that miR-215-5p may modulate cell survival programs by regulating autophagy, and miR-215-5p acts as an autophagic regulator in the regulatory feedback loop that regulates cardiomyocyte survival by modulating the PI3K/AKT/TOR pathway and ROS-dependent MAPK pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2019.01.010DOI Listing
April 2019

Selenium deficiency inhibits myocardial development and differentiation by targeting the mir-215-5p/CTCF axis in chicken.

Metallomics 2019 02;11(2):415-428

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.

Selenium (Se) is imperative for normal myocardial differentiation and development, and these basic cellular functions can be regulated by miRNA during cardiogenesis. Here, we show that Se deficiency can cause defects in myocardial development and abnormalities of cardiomyocyte differentiation. In previous work using microRNAome analysis, we found that miR-215-5p was differentially expressed in Se-deficient myocardial tissues. However, the relationship between miR-215-5p and Se deficiency in myocardial development remains unknown. In this study, CCCTC-binding factor (CTCF) was confirmed as the target gene of miR-215-5p by dual luciferase reporter assay, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) in cardiomyocytes. Based on in vivo and in vitro results, we found that the increased expression of miR-215-5p induced by Se deficiency may cause transcriptional disorders of myocardial genes, mitochondrial biosynthesis imbalance, and a reduction of myocardial development and differentiation-related factors. Moreover, miR-215-5p may target CTCF to regulate myocardial development and differentiation via the noncanonical Wnt signaling pathway and induce mitochondrial dysfunction via the PGC-1α-TFAM-NRF1/2 pathway in the heart. Our results not only demonstrated that Se deficiency affected myocardial development and differentiation by directly targeting the miR-215-5p/CTCF axis but also found that miR-215-5p inhibitor promoted normal differentiation of cardiomyocytes and myocardial development and ameliorated myocardium structural abnormalities via the noncanonical Wnt signaling pathway in chicken. Our findings support the potential of applying miRNAs during the process of cardiogenesis and indicate that miR-215-5p could be a novel candidate for treatment of cardiac hypoevolutism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8mt00319jDOI Listing
February 2019

Effect of Gpx3 gene silencing by siRNA on apoptosis and autophagy in chicken cardiomyocytes.

J Cell Physiol 2019 06 4;234(6):7828-7838. Epub 2018 Dec 4.

Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Glutathione peroxidase 3 (Gpx3), as an important selenoprotein, is the most crucial antioxidant defense in cardiomyocytes. However, the role of Gpx3 in Se-deficient cardiomyocyte damage still less reported. Here, we developed Gpx3 silence cardiomyocytes culture model (small interfering RNA; siRNA) for research the crosstalk between autophagy and apoptosis. Quantitative real-time PCR and western blot analysis are performed to detect the expression of apoptosis and autophagy-related genes. MDC stain, flow cytometry, AO/EB stain, and electron microscope were performed to observe the changes of cell morphology. Our results reveal that Gpx3 suppression can significant increases in ROS (p < 0.05) levels, which further induced apoptosis through upregulated the expression of Caspase-3 in cardiomyocytes. Meanwhile, we also found that the whole process is accompanied by the occurrence of autophagy, which are promoted by inhibiting the mTOR, and increasing the expression of ATG-7, ATG-10, and ATG-12. Altogether, we conclude that the apoptotic and autophagic response machineries share antagonistic function in Gpx3 knockdown cardiomyocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27842DOI Listing
June 2019

miR-2954 Inhibits PI3K Signaling and Induces Autophagy and Apoptosis in Myocardium Selenium Deficiency.

Cell Physiol Biochem 2018 21;51(2):778-792. Epub 2018 Nov 21.

College of Veterinary Medicine, Northeast Agricultural University, Harbin,

Background/aims: Selenium (Se) deficiency can lead to several cardiac diseases, including Keshan disease in humans, mulberry heart disease in pigs and cardiac injury in chickens. MicroRNAs have been a research focus in recent years and have been shown to participate in a new avenue of cell death-autophagy, which can play a significant role in several types of heart disease.

Methods: MicroRNAome analysis showed that the expression of miR-2954 was increased in the myocardium of selenium-deficient chickens, and PI3K was predicted to be the target gene. The target relationship between miR-2954 and PI3K was verified with a double fluorescence enzyme assay and RNA Protein Interaction Prediction and molecular docking software. qRT-PCR and western blotting were used to detect the expression of PI3K and related pathway components in selenium-deficient chickens and miR-2954 knockout/overexpression cardiomyocytes.

Results: In this study, we observed that miR-2954 overexpression led to inhibition of PI3K pathway in vivo and in vitroled to inhibition of the PI3K pathway in vivo and in vitro.

Conclusion: The expression of miR-2954 was increased in selenium-deficient myocardium, whereas overexpression of miR-2954 led to autophagy and apoptosis of myocardial cells during cardiac injury through regulation of the PI3K pathway; whether this phenomenon is a self-protection mechanism of the organism or damage caused by miR-2954 requires further study. Our findings provides new insight apoptosis in cardiomyocytes; additionally, we aim to provide a new direction for the diagnosis and targeted treatment of myocardial diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000495332DOI Listing
December 2018

Thioredoxin silencing-induced cardiac supercontraction occurs through endoplasmic reticulum stress and calcium overload in chicken.

Metallomics 2018 11;10(11):1667-1677

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.

The thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in the myocardium, and hampering the Txn system may compromise cell survival. Calcium (Ca) imbalance is associated with a variety of cardiomyopathies, and dysregulation of Ca2+ homeostasis is often considered a critical starting point for heart disease. However, the roles of Txn and the Txn system in maintaining Ca2+ homeostasis in cardiomyocytes have been infrequently reported. Here, we examined the expression of genes associated with Ca2+ channels using a model of Txn suppression in cardiomyocyte cultures (siRNA and Txn inhibitor) and report that Txn knockdown can cause Ca2+ overload in the myocardial cytoplasm and release of endoplasmic reticulum (ER) Ca2+, which induces ER stress. Our results showed that Txn knockdown could lead to cytosolic Ca2+ overload through upregulated gene expression of Ca2+ channel-related genes in the cytoplasmic and ER membranes. Furthermore, we find that excessive Ca2+ concentrations in the cytoplasm may increase myocardial contraction, and heat shock proteins may play a protective role throughout the process. Our present study reveals a novel model of regulation for low Txn expression in myocardial injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8mt00206aDOI Listing
November 2018

Selenoprotein-U (SelU) knockdown triggers autophagy through PI3K-Akt-mTOR pathway inhibition in rooster Sertoli cells.

Metallomics 2018 07;10(7):929-940

College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin 150030, P. R. China.

Selenium (Se) is a major component of male reproduction which exerts its effects via selenoproteins. Selenoprotein U (SelU), a newly identified protein, is expressed highly in eukaryotes and possesses a conserved motif similar to that existing in other thiol-dependent redox regulating selenoproteins; however its function is unknown. To investigate the role of SelU in testis autophagic and/or apoptosis cell death mechanisms, we established a Sertoli cell (SC) model isolated from 45 day old layer roosters. Small interfering RNA (siRNA) technology was used to develop SelU-knockdown (SelU-KD) and normal (N) SC models. Consequent to transfection, electron microscopy, qPCR, and western blot were performed. The results show that the mRNA and proteins of autophagy and anti-apoptosis genes increased while that of anti-autophagic mammalian target of rapamycin (mTOR) and pro-apoptosis genes decreased significantly in SelU-KD in contrast to N cells. Simultaneously, in contrast to N cells the expression of phosphoinositide-3-kinase (PI3K) and protein kinase B (PKB/Akt) both at the mRNA and protein levels decreased significantly in SelU-KD cells. In-addition, SelU depletion altered the expression of regulatory factors and increased the mRNA of TSC (tuberous sclerosis complex) genes as compared to N cells. Extensive autophagosome formation and lysosome degradation with an intact cytoskeleton were observed in SelU-KD cells. Our data indicate that SelU deprivation elicits autophagy and reduces the expression of important growth factors in SCs by disrupting the PI3K-Akt-mTOR signaling pathway. However SelU attenuation did not induce apoptosis in rooster SCs. Taken together, we conclude that SelU is essential for the survival and normal functioning of SCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8mt00090eDOI Listing
July 2018

The Antagonistic Effect of Selenium on Lead-Induced Immune Dysfunction via Recovery of Cytokine and Heat Shock Protein Expression in Chicken Neutrophils.

Biol Trace Elem Res 2018 Sep 20;185(1):162-169. Epub 2017 Dec 20.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Lead (Pb) is a ubiquitous and toxic heavy metal and it can damage the immune system in humans and animals. Many researchers have reported that Selenium (Se) could possess various pharmacological effects in mammals. However, few studies have been carried out to investigate the protective role of Se in birds, especially in chickens. In this study, we investigated the protective effects of Se against Pb-induced inflammatory responses and the expression of heat shock proteins (HSPs) in peripheral blood neutrophils. One hundred eighty Hy-Line brown chickens were randomly divided into the control group (Con group), Se supplementation group (+Se group), Pb supplementation group (+Pb group), and the Se and Pb compound group (Se+Pb group). On the 90th day of the experiment, the peripheral blood was collected to extract neutrophils, and then, the levels of HSPs and cytokines were examined. The results showed that, after Pb treatment, the levels of IL-(1β, 1R, 4, 8, 10, and 12β), TGF-β4, and HSP (27, 40, 60, 70, and 90) mRNA were significantly increased and levels of IL-2 and IFN-γ mRNA were decreased compared with those in the control group. Compared with the control group, the protein levels of HSP60 and HSP70 were also increased in the Pb treatment group. Co-administration of Se (1 mg/kg/day) and Pb resulted in a reversal of the Pb-induced cytokine changes in neutrophils accompanied by a significant decrease in HSPs. Our study demonstrated that Pb could decrease the immune function via changing the expression of cytokines and HSPs in chicken neutrophils, but Se could relieve the toxic effect induced by Pb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-017-1200-2DOI Listing
September 2018

Effect of cadmium on oxidative stress and immune function of common carp (Cyprinus carpio L.) by transcriptome analysis.

Aquat Toxicol 2017 Nov 23;192:171-177. Epub 2017 Sep 23.

Department of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cadmium (Cd) is an increasingly important environmental pollutant which causes irreversible toxicity to fish. To understand how Cd impacts the immune response and oxidative stress in common carp, we performed transcriptomic profiles for head kidney, the immune organ of common carp which were underwent Cd exposure. Totally there are 42,489,124 and 48,562,526 high quality clean reads obtained from the Cd exposure groups, and 44,677,578 and 44,106,696 clean reads from the control groups. Among them, 308 genes were differently expressed, including 101 upregulated and 207 down-regulated genes. The identified genes were enriched using databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems and immune function genes and pathways were identified and validated by quantitative real-time RT-PCR. Our results showed that Cd exposure leads to oxidative stress and immunosuppression in head kidney of common carp. These results provide new insights for unveiling the biological effects of Cd in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2017.09.022DOI Listing
November 2017

Gene expression of selenoproteins can be regulated by thioredoxin(Txn) silence in chicken cardiomyocytes.

J Inorg Biochem 2017 12 4;177:118-126. Epub 2017 Sep 4.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in myocardium. The aim of this study was to clarify the effect of Txn low expression on 25 selenoproteins in chicken cardiomyocytes. We developed a Se-deficient model (0.033mg/kg) and Txn knock down cardiomyocytes model (siRNA) studies. Western Blot, Quantitative Real-time PCR (qPCR) were performed, and correlation analysis, heat map were used for further analysis. Both low expression of Txn models are significantly decreased (P<0.05) the mRNA levels of Deiodinase 1, 2 (Dio 1, 2), Glutathione Peroxidase 1, 2, 3, 4 (Gpx 1, 2, 3, 4), Thioredoxin Reductase 1, 2, 3 (TR 1, 2, 3), Selenoprotein t (Selt), Selenoprotein w (Selw), Selenoprotein k (Selk), selenoprotein x1 (Sepx1), and significantly increased (P<0.05) the mRNA levels of the rest of selenoproteins. Correlation analysis showed that Deiodinase 3 (Dio 3), Selenoprotein m (Selm), 15-kDa Selenoprotein (Selp15), Selenoprotein h (Selh), Selenoprotein u (Selu), Selenoprotein i (Seli), Selenoprotein n (Seln), Selenoprotein p1 (Sepp1), Selenoprotein o (Selo), Selenoprotein s (Sels), Selenoprotein synthetase 2 (Sels2) and Selenoprotein p (Selp) had a negative correlation with Txn, while the rest of selenoproteins had a positive correlation with Txn. Combined in vivo and in vitro we can know that hamper Txn expression can inhibit Gpx 1, 2, 3, 4, TR 1, 2, 3, Dio 1, 2, Selt, Selw, Selk, Sepx1, meanwhile, over expression the rest of selenoproteins. In conclusion, the different selenoproteins possess and exhibit distinct responses to silence of Txn in chicken cardiomyocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2017.08.027DOI Listing
December 2017

Selenium deficiency-induced thioredoxin suppression and thioredoxin knock down disbalanced insulin responsiveness in chicken cardiomyocytes through PI3K/Akt pathway inhibition.

Cell Signal 2017 10 19;38:192-200. Epub 2017 Jul 19.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in cell consisting of Txn, thioredoxin reductase (TR) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH). Perturbations in Txn system may compromise cell survival through oxidative stress induction. Metabolic activity of insulin plays important roles in fulfilling the stable and persistent demands of heart through glucose metabolism. However, the roles of Txn and Txn system in insulin modulated cardiac energy metabolism have been less reported. Therefore, to investigate the role of Txn in myocardial metabolism, we developed a Se-deficient chicken model (0.033mg/kg) for in-vivo and Txn knock down cardiomyocytes culture model (siRNA) for in-vitro studies. Quantitative real time PCR and western blotting was performed. Se deficiency suppressed Txn and TR in cardiac tissues. Significant increases in ROS (P<0.05) levels signify the onset of oxidative stress and in both models. Se deficiency-induced Txn suppression model and Txn knock down cardiomyocytes models significantly decreased (P<0.05), the mRNA and protein levels of insulin-like growth factors (IGF1, IGF2), IGF-binding proteins (IGFBP2, IGFBP4), insulin receptor (IR), insulin receptor substrates (IRS1, IRS2), and glucose transporters (GLUT1, GLUT3, GLUT8), however, IGFBP3 expression increased in Txn knock down cardiomyocytes. In addition, in contrast to their respective controls, Se deficiency-induced Txn depleted tissues and Txn deleted cardiomyocytes showed suppression in mRNA and protein levels of PI3K, AKT, P-PI3K, and repression in FOX, P-FOX JNK genes. Combing the in vitro and in vivo experiments, we demonstrate that Txn gene suppression can cause dysfunction of insulin-modulated cardiac energy metabolism and increase insulin resistance through PI3K-Akt pathway inhibition. Herein, we conclude that inactivation of Txn system can alter cellular insulin response through IRS/PI3K/Akt pathway repression and JNK and FOX expression. These findings point out that Txn system can redox regulate the insulin dependent glucose metabolism in heart and is essential for cell vitality. Moreover, the increased expression of IGFBP3 indicates that it can be a potential negative modulator of metabolic activity of insulin in Txn deficient cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2017.07.012DOI Listing
October 2017

Chlorpyrifos exposure in common carp (Cyprinus carpio L.) leads to oxidative stress and immune responses.

Fish Shellfish Immunol 2017 Aug 22;67:604-611. Epub 2017 Jun 22.

Department of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Chlorpyrifos (CPF) is an environmental pollutant with increasing importance due to its high toxicity to fish and aquatic animals. To understand how CPF impacts immune response and oxidative stress in common carp (Cyprinus carpio L.), we investigated the transcriptomic profiles of the head kidneys from common carp exposed to CPF for 15days. A total of 52, 297, 928 and 52, 273, 784 high quality clean reads were obtained from CPF exposure groups, 44,677,578 and 44,106,696 high quality clean reads were obtained from corresponding control groups. Among them, 456 genes were differentially expressed, including 246 up-regulated genes and 210 down-regulated genes identified and enriched in databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems, and immune response genes and pathways were verified by quantitative real-time RT-PCR. We found that CPF-induced ROS regulates immune response by stimulating the antigen-presenting ability of head kidney in carp. These results provide new insights for unveiling the biological effects of CPF in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2017.06.048DOI Listing
August 2017

Analysis of the Interactions Between Thioredoxin and 20 Selenoproteins in Chicken.

Biol Trace Elem Res 2017 Oct 2;179(2):304-317. Epub 2017 Mar 2.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Thioredoxin (Trx) is a small molecular protein with complicated functions in a number of processes, including inflammation, apoptosis, embryogenesis, cardiovascular disease, and redox regulation. Some selenoproteins, such as glutathione peroxidase (Gpx), iodothyronine deiodinase (Dio), and thioredoxin reductase (TR), are involved in redox regulation. However, whether there are interactions between Trx and selenoproteins is still not known. In the present paper, we used a Modeller, Hex 8.0.0, and the KFC2 Server to predict the interactions between Trx and selenoproteins. We used the Modeller to predict the target protein in objective format and assess the accuracy of the results. Molecular interaction studies with Trx and selenoproteins were performed using the molecular docking tools in Hex 8.0.0. Next, we used the KFC2 Server to further test the protein binding sites. In addition to the selenoprotein physiological functions, we also explored potential relationships between Trx and selenoproteins beyond all the results we got. The results demonstrate that Trx has the potential to interact with 19 selenoproteins, including iodothyronine deiodinase 1 (Dio1), iodothyronine deiodinase 3 (Dio3), glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), glutathione peroxidase 3 (Gpx3), glutathione peroxidase 4 (Gpx4), selenoprotein H (SelH), selenoprotein I (SelI), selenoprotein M (SelM), selenoprotein N (SelN), selenoprotein T (SelT), selenoprotein U (SelU), selenoprotein W (SelW), selenoprotein 15 (Sep15), methionine sulfoxide reductase B (Sepx1), selenophosphate synthetase 1 (SPS1), TR1, TR2, and TR3, among which TR1, TR2, TR3, SPS1, Sep15, SelN, SelM, SelI, Gpx2, Gpx3, Gpx4, and Dio3 exhibited intense correlations with Trx. However, additional experiments are needed to verify them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-017-0961-yDOI Listing
October 2017
-->