171 results match your criteria p32 levels

Overexpression of Multifunctional Protein p32 Promotes a Malignant Phenotype in Colorectal Cancer Cells.

Front Oncol 2021 31;11:642940. Epub 2021 May 31.

Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.

p32 is a multifunctional and multicompartmental protein that has been found upregulated in numerous adenocarcinomas, including colorectal malignancy. High levels of p32 expression have been correlated with poor prognosis in colorectal cancer. However, the functions performed by p32 in colorectal cancer have not been characterized. Read More

View Article and Full-Text PDF

Arginase inhibition by rhaponticin increases L-arginine concentration that contributes to Ca2+-dependent eNOS activation.

BMB Rep 2021 Jun 3. Epub 2021 Jun 3.

Department of Biological Sciences, Kangwon National University, Chuncheon 24341, Korea.

Although arginase primarily participates in the last reaction of the urea cycle, we have previously demonstrated that arginase II is an important cytosolic calcium regulator through spermine production in a p32-dependent manner. Here, we demonstrated that rhaponticin (RPT) is a novel medicinal-plant arginase inhibitor and investigated its mechanism of action on Ca2+-dependent endothelial nitric oxide synthase (eNOS) activation. RPT was uncompetitively inhibited for both arginases I and II prepared from mouse liver and kidney. Read More

View Article and Full-Text PDF

Arginase II protein regulates Parkin-dependent p32 degradation that contributes to Ca2+-dependent eNOS activation in endothelial cells.

Cardiovasc Res 2021 May 8. Epub 2021 May 8.

Department of Biological Sciences.

Aims: Arginase II (ArgII) plays a key role in the regulation of Ca2+ between the cytosol and mitochondria in a p32-dependent manner. p32 contributes to endothelial nitric oxide synthase (eNOS) activation through the Ca2+/CaMKII/AMPK/p38MAPK/Akt signaling cascade. Therefore, we investigated a novel function of ArgII in the regulation of p32 stability. Read More

View Article and Full-Text PDF

Novel drug resistance-associated substitutions against pibrentasvir emerged in genotype 1b hepatitis C virus-infected human hepatocyte transplanted mice.

Biochem Biophys Res Commun 2021 Jun 29;559:78-83. Epub 2021 Apr 29.

Department of Gastroenterology and Metabolism, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan; Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan; Institute of Physical and Chemical Research (RIKEN) Center for Integrative Medical Sciences, Yokohama, Japan. Electronic address:

Combination therapy with glecaprevir and pibrentasvir (PIB) has high efficacy for patients with hepatitis C virus (HCV) infection except among those who experienced NS5A-P32 deletion (del) mutation during prior DAA treatment failure. However, some patients fail to achieve SVR through combination treatment even in the absence of NS5A-P32del. We analyzed emergence of NS5A resistance-associated substitutions (RASs) against PIB using HCV-infected mice. Read More

View Article and Full-Text PDF

Heterozygous // Polymorphism Reduces Mitochondrial Oxidative Phosphorylation and Is Expressed in Low-grade Colorectal Carcinomas.

Front Oncol 2020 8;10:631592. Epub 2021 Feb 8.

Institute of Nutritional Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Rapid proliferation of cancer cells is enabled by favoring aerobic glycolysis over mitochondrial oxidative phosphorylation (OXPHOS). P32 (/gC1qR) is essential for mitochondrial protein translation and thus indispensable for OXPHOS activity. It is ubiquitously expressed and directed to the mitochondrial matrix in almost all cell types with an excessive up-regulation of p32 expression reported for tumor tissues. Read More

View Article and Full-Text PDF
February 2021

Protective immune response against P32 oncogenic peptide-pulsed PBMCs in mouse models of breast cancer.

Int Immunopharmacol 2021 Apr 9;93:107414. Epub 2021 Feb 9.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

High expression of p32 in certain tumors makes it a potential target for immunotherapy. In the present study, the first goal was to design multi-epitope peptides from the P32 protein and the second goal was to compare the prophylactic effects of DCs- and PBMCs- based vaccines by pulsing them with designed peptides. For these purposes, 160 BALB/c mice were vaccinated in 5 different subgroups of each 4 peptides using PBS (F1-4a), F peptides alone (F1-4b), F peptides with CpG-ODN (F1-4c), F peptides with CpGODN and DCs (F1-4d), and F peptides with CpG-ODN and PBMCs (F1-4e). Read More

View Article and Full-Text PDF

Mitochondrial translation deficiency impairs NAD -mediated lysosomal acidification.

EMBO J 2021 Apr 2;40(8):e105268. Epub 2021 Feb 2.

Department of Clinical Chemistry and Laboratory Medicine, Kyushu University, Fukuoka, Japan.

Mitochondrial translation dysfunction is associated with neurodegenerative and cardiovascular diseases. Cells eliminate defective mitochondria by the lysosomal machinery via autophagy. The relationship between mitochondrial translation and lysosomal function is unknown. Read More

View Article and Full-Text PDF

Pathogenic mutations reveal a role of RECQ4 in mitochondrial RNA:DNA hybrid formation and resolution.

Sci Rep 2020 10 12;10(1):17033. Epub 2020 Oct 12.

Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.

The synthesis of mitochondrial DNA (mtDNA) is a complex process that involves the formation and resolution of unusual nucleic acid structures, such as RNA:DNA hybrids. However, little is known about the enzymes that regulate these processes. RECQ4 is a DNA replication factor important for mtDNA maintenance, and here, we unveil a role of human RECQ4 in regulating the formation and resolution of mitochondrial RNA:DNA hybrids. Read More

View Article and Full-Text PDF
October 2020

Localized Prediction of Glutamate from Whole-Brain Functional Connectivity of the Pregenual Anterior Cingulate Cortex.

J Neurosci 2020 11 12;40(47):9028-9042. Epub 2020 Oct 12.

Max Planck Institute for Biological Cybernetics, 72076 Tübingen, Germany

Local measures of neurotransmitters provide crucial insights into neurobiological changes underlying altered functional connectivity in psychiatric disorders. However, noninvasive neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may cover anatomically and functionally distinct areas, such as and of the pregenual anterior cingulate cortex (pgACC). Here, we aimed to overcome this low spatial specificity of MRS by predicting local glutamate and GABA based on functional characteristics and neuroanatomy in a sample of 88 human participants (35 females), using complementary machine learning approaches. Read More

View Article and Full-Text PDF
November 2020

Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses.

Aging Cell 2020 10 22;19(10):e13222. Epub 2020 Aug 22.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Sumoylation is one of the key regulatory mechanisms in eukaryotes. Our previous studies reveal that sumoylation plays indispensable roles during lens differentiation (Yan et al. 2010. Read More

View Article and Full-Text PDF
October 2020

Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma.

Front Immunol 2020 14;11:1292. Epub 2020 Jul 14.

Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Read More

View Article and Full-Text PDF

Overexpressed p32 localized in the endoplasmic reticulum and mitochondria negatively regulates calcium‑dependent endothelial nitric oxide synthase activit.

Mol Med Rep 2020 Sep 6;22(3):2395-2403. Epub 2020 Jul 6.

Department of Biological Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.

The p32 protein plays a crucial role in the regulation of cytosolic Ca2+ concentrations ([Ca2+]c) that contributes to the Ca2+‑dependent signaling cascade. Using an adenovirus and plasmid p32‑overexpression system, the aim of the study was to evaluate the role of p32 in the regulation of [Ca2+] and its potential associated with Ca2+‑dependent endothelial nitric oxide synthase (eNOS) activation in endothelial cells. Using electron and confocal microscopic analysis, p32 overexpression was observed to be localized to mitochondria and the endoplasmic reticulum and played an important role in Ca2+ translocation, resulting in increased [Ca2+] in these organelles and reducing cytosolic [Ca2+] ([Ca2+]c). Read More

View Article and Full-Text PDF
September 2020

LyP-1-Modified Oncolytic Adenoviruses Targeting Transforming Growth Factor β Inhibit Tumor Growth and Metastases and Augment Immune Checkpoint Inhibitor Therapy in Breast Cancer Mouse Models.

Hum Gene Ther 2020 08 12;31(15-16):863-880. Epub 2020 Jun 12.

Gene Therapy Program, Department of Medicine, NorthShore Research Institute, An Affiliate of the University of Chicago, Evanston, Illinois, USA.

We report here the development of oncolytic adenoviruses (Ads) that have reduced toxicity, enhanced tumor tropism, produce strong antitumor response, and can overcome resistance to immune checkpoint inhibitor therapy in breast cancer. We have shown that LyP-1 receptor (p32) is highly expressed on the surface of breast cancer cells and tumors from cancer patients, and that increased stromal expression of transforming growth factor β-1 (TGFβ-1) is associated with triple-negative breast cancer. Therefore, we constructed oncolytic Ads, AdLyp. Read More

View Article and Full-Text PDF

Complement Receptor Targeted Liposomes Encapsulating the Liver X Receptor Agonist GW3965 Accumulate in and Stabilize Atherosclerotic Plaques.

Adv Healthc Mater 2020 05 24;9(10):e2000043. Epub 2020 Apr 24.

Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, 2333CC, The Netherlands.

Atherosclerosis is characterized by the retention of lipids in foam cells in the arterial intima. The liver X receptor (LXR) agonist GW3965 is a promising therapeutic compound, since it induces reverse cholesterol transport in foam cells. However, hepatic LXR activation increases plasma and liver lipid levels, inhibiting its clinical development. Read More

View Article and Full-Text PDF

Long-term evaluation of retinal morphology and function in a mouse model of oxygen-induced retinopathy.

Mol Vis 2020 1;26:257-276. Epub 2020 Apr 1.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Purpose: Retinopathy of prematurity (ROP) is a condition of aberrant retinal vascularization in premature infants in response to high levels of oxygen used for critical care that can potentially cause blindness. Although therapies to mitigate vascular abnormalities are being evaluated, functional deficits often remain in patients with treated or regressed ROP. This study investigated long-term outcomes of hyperoxia on retinal morphology and function using a mouse model of oxygen-induced ischemic retinopathy (OIR). Read More

View Article and Full-Text PDF
February 2021

Chchd2 regulates mitochondrial morphology by modulating the levels of Opa1.

Cell Death Differ 2020 06 6;27(6):2014-2029. Epub 2020 Jan 6.

The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, Hangzhou, China.

The mitochondrion is a highly dynamic organelle that is critical for energy production and numerous metabolic processes. Drosophila Chchd2, a homolog of the human disease-related genes CHCHD2 and CHCHD10, encodes a mitochondrial protein. In this study, we found that loss of Chchd2 in flies resulted in progressive degeneration of photoreceptor cells and reduced muscle integrity. Read More

View Article and Full-Text PDF

p32 is a negative regulator of p53 tetramerization and transactivation.

Mol Oncol 2019 09 30;13(9):1976-1992. Epub 2019 Jul 30.

Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

p53 is a sequence-specific transcription factor, and proper regulation of p53 transcriptional activity is critical for orchestrating different tumor-suppressive mechanisms. p32 is a multifunctional protein which interacts with a large number of viral proteins and transcription factors. Here, we investigate the effect of p32 on p53 transactivation and identify a novel mechanism by which p32 alters the functional characteristics of p53. Read More

View Article and Full-Text PDF
September 2019

Arginase II activity regulates cytosolic Ca level in a p32-dependent manner that contributes to Ca-dependent vasoconstriction in native low-density lipoprotein-stimulated vascular smooth muscle cells.

Exp Mol Med 2019 06 3;51(6):1-12. Epub 2019 Jun 3.

Department of Biology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.

Although arginase II (ArgII) is abundant in mitochondria, Ca-accumulating organelles, the relationship between ArgII activity and Ca translocation into mitochondria and the regulation of cytosolic Ca signaling are completely unknown. We investigated the effects of ArgII activity on mitochondrial Ca uptake through mitochondrial p32 protein (p32m) and on CaMKII-dependent vascular smooth muscle cell (VSMC) contraction. Native low-density lipoprotein stimulation induced an increase in [Ca]m as measured by CoCl-quenched calcein-AM fluorescence, which was prevented by Arg inhibition in hAoSMCs and reduced in mAoSMCs from ArgII mice. Read More

View Article and Full-Text PDF

Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients.

Sci Rep 2019 04 5;9(1):5722. Epub 2019 Apr 5.

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) in the NS5A region impair the efficacy of NS5A inhibitors. In this study, we evaluated the characteristics of the novel RASs observed in treatment-failure patients, A92K and a deletion at P32 (P32del), and the susceptibility of viruses with these RASs to various anti-HCV reagents by using JFH-1 based recombinant HCV with NS5A from a genotype 1b Con1 strain (JFH1/5ACon1). We introduced A92K or P32del solely or in combination with Q24K, L28M, R30Q or L31F into the NS5A of JFH1/5ACon1. Read More

View Article and Full-Text PDF

Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice.

J Gastroenterol 2019 May 25;54(5):449-458. Epub 2019 Jan 25.

Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: The emergence of a deletion mutant at hepatitis C virus (HCV) NS5A-P32 (P32del) has recently been reported in a subset of chronic hepatitis C patients who experience virologic failure after direct-acting antiviral drug (DAA) treatment. This mutation confers extremely high resistance to NS5A inhibitors. No effective treatment has been established for cases with this mutation. Read More

View Article and Full-Text PDF

Analysis of Non-Sumoylated and Sumoylated Isoforms of Pax-6, the Master Regulator for Eye and Brain Development in Ocular Cell Lines.

Curr Mol Med 2018 ;18(8):566-573

The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, #7 Jinsui Road, Guangzhou, Guangdong 510230, China.

Purpose: Pax-6 is a master regulator for eye and brain development. Previous studies including ours have shown that Pax-6 exists in 4 major isoforms. According to their sizes, they are named p48, p46, p43 and p32 with the corresponding molecular weight of 48, 46, 43 and 32 kd, respectively. Read More

View Article and Full-Text PDF
October 2019

Zinc/CaMK II Associated-Mitophagy Signaling Contributed to Hippocampal Mossy Fiber Sprouting and Cognitive Deficits Following Neonatal Seizures and Its Regulation by Chronic Leptin Treatment.

Front Neurol 2018 26;9:802. Epub 2018 Sep 26.

Neurology Laboratory, Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.

The role of leptin in the pathogenesis of epilepsy is getting more and more attention in clinical and basic research. Although there are data indicating neuroprotective effects of elevated serum/brain leptin levels following acute seizures, no study to date has dealt with the impact of chronic leptin treatment on long-term brain injury following developmental seizures. The aim of this study was to evaluate whether chronic leptin treatment may have neuroprotective effects on cognitive and hippocampal mossy fiber sprouting following flurothyl-induced recurrent neonatal seizures and whether these effects are mediated by the zinc/CaMKII-associated mitophagy signaling pathway. Read More

View Article and Full-Text PDF
September 2018

Mycorrhizal inoculation as an alternative for the sustainable production of Mimosa tenuiflora seedlings with improved growth and secondary compounds content.

Fungal Biol 2018 09 6;122(9):918-927. Epub 2018 Jun 6.

Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Pernambuco, Centro de Biociências, 50740-600, Recife, PE, Brazil; Programa de Pós-Graduação em Biologia de Fungos, Universidade Federal dePernambuco, Centro de Biociências, Departamento de Micologia, 50740-600, Recife, PE, Brazil. Electronic address:

In this study, we report the effects of arbuscular mycorrhizal fungi (AMF) and increasing doses of phosphorus (P) on the growth and production of secondary metabolites in Mimosa tenuiflora, a medicinal species native to Brazil. We used a completely randomized design with four inoculation treatments: Control not inoculated (1); Claroideoglomus etunicatum (2); Gigaspora albida (3); and C. etunicatum + G. Read More

View Article and Full-Text PDF
September 2018

The achievement of boar sperm in vitro capacitation is related to an increase of disrupted disulphide bonds and intracellular reactive oxygen species levels.

Andrology 2018 09 12;6(5):781-797. Epub 2018 Aug 12.

Department of Animal Medicine and Surgery, Autonomous University of Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.

The aim of this work was to determine the relationship of intracellular reactive oxygen species (ROS) and the disulphide bonds established between sperm proteins with the achievement of capacitation in boar spermatozoa. With this purpose, spermatozoa were incubated in a specifically designed in vitro capacitation medium (CM) in the presence or absence of reduced glutathione (GSH). Incubation of boar spermatozoa in CM for 4 h significantly (p < 0. Read More

View Article and Full-Text PDF
September 2018

Cellular stress and AMPK activation as a common mechanism of action linking the effects of metformin and diverse compounds that alleviate accelerated aging defects in Hutchinson-Gilford progeria syndrome.

Jahahreeh Finley

Med Hypotheses 2018 Sep 28;118:151-162. Epub 2018 Jun 28.

Finley BioSciences, Houston, TX 77042-4539, United States. Electronic address:

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6 years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Read More

View Article and Full-Text PDF
September 2018

Manipulating excited state hyperfine level populations in an atomic laser through electronic spin polarization: controlling upper laser level degeneracy and small Signal Gain.

Opt Express 2017 Nov;25(24):29676-29686

Anisotropic coherent radiation has been generated from an isotropic medium, in the absence of an external magnetic field, by the spin polarization of an atomic excited state. Lasing on specific hyperfine lines of the 6pP→6sS (D) transition of Cs at 852.1 nm has been realized by photoexciting Cs-rare gas thermal collision pairs with a circularly-polarized (σ) optical field. Read More

View Article and Full-Text PDF
November 2017

Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies.

Am J Hum Genet 2017 Oct 21;101(4):525-538. Epub 2017 Sep 21.

Department of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan.

Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure. Read More

View Article and Full-Text PDF
October 2017

Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses.

Cardiovasc Res 2017 Aug;113(10):1173-1185

Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan.

Aims: Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. Read More

View Article and Full-Text PDF

Effect of Co-overexpression of Nisin Key Genes on Nisin Production Improvement in Lactococcus lactis LS01.

Probiotics Antimicrob Proteins 2017 06;9(2):204-212

Institute of Biochemical and Biotechnological Drugs, College of Pharmacy, Shandong University, Jinan, 250012, People's Republic of China.

Nisin is a small antimicrobial peptide produced by several subset strains of Lactococcus lactis. To improve nisin yield in the producer L. lactis LS01, we proposed a successive fusion of nisA with nisRK and nisFEG into a single shuttle expression vector pMG36e under the control of the native strong constitutive promoter p32. Read More

View Article and Full-Text PDF

The effects of repeated forced ethanol consumption during adolescence on reproductive behaviors in male rats.

Alcohol 2016 09 16;55:61-68. Epub 2016 Sep 16.

Dept. of Psychology, Fairfield University, Fairfield, CT, USA.

Adolescence is a sensitive period of brain development when changes in hormone levels may have long-lasting effects on synaptic connections and behavior. In humans, alcohol consumption frequently begins during this critical period, although the impact of early exposure has not been fully examined. The current study was designed to investigate short- and long-term effects of repeated forced ethanol consumption during adolescence on emerging reproductive behaviors. Read More

View Article and Full-Text PDF
September 2016