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Glutathione S-transferase, alpha 4

GSTA4, mGSTA4-4, GSTA4-4, hGSTA4-4, mGSTA4
Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: GST, Leukocyte Elastase, CAN, ACID, HAD
Papers on GSTA4
Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells.
Alshatwi et al., Riyadh, Saudi Arabia. In Cell Biol Toxicol, Apr 2014
The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied.
Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.
Laskin et al., United States. In Toxicol Appl Pharmacol, Apr 2014
Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4.
Regulation of keratinocyte expression of stress proteins and antioxidants by the electrophilic nitrofatty acids 9- and 10-nitrooleic acid.
Laskin et al., United States. In Free Radic Biol Med, Feb 2014
Treatment of keratinocytes with 5-25μM 9-NO or 10-NO for 6h upregulated mRNA expression of heat shock proteins (hsp's) 27 and 70; primary antioxidants heme oxygenase-1 (HO-1) and catalase; secondary antioxidants glutathione S-transferase (GST) A1/2, GSTA3, and GSTA4; and Cox-2, a key enzyme in prostaglandin biosynthesis.
A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy.
Johnson et al., London, United Kingdom. In Hum Mol Genet, Feb 2014
Genes of biological interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated in neuronal development) and GSTA4 (a phase II biotransformation enzyme).
Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice.
Klaassen et al., Kansas City, United States. In Toxicol Appl Pharmacol, Feb 2014
CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2).
Glutathionylated lipid aldehydes are products of adipocyte oxidative stress and activators of macrophage inflammation.
Bernlohr et al., Minneapolis, United States. In Diabetes, Jan 2014
Trans-4-hydroxy-2-nonenal (4-HNE) is the most abundant lipid aldehyde in murine adipose tissue and is metabolized by glutathione S-transferase A4 (GSTA4), producing glutathionyl-HNE (GS-HNE) and its metabolite glutathionyl-1,4-dihydroxynonene (GS-DHN).
Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.
Stordal et al., Dublin, Ireland. In Anticancer Res, Jan 2014
KB-8-5-11 had decreased gene expression of glutathione S-transferase pi 1 (GSTP1), GSTA4 and GSTK1.
Gene expression within the extended amygdala of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
Bell et al., Indianapolis, United States. In Alcohol, Nov 2013
There were 4-6 individual named genes that significantly differed across up to 3 line-pairs in both regions; only 1 gene (Gsta4 in the CeA) differed in as many as 4 line-pairs.
Gsta4 Null Mouse Embryonic Fibroblasts Exhibit Enhanced Sensitivity to Oxidants: Role of 4-Hydroxynonenal in Oxidant Toxicity.
Singh et al., Little Rock, United States. In Open J Apoptosis, 2013
UNLABELLED: The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.18)
Down-regulation of glutatione S-transferase α 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection.
Rahme et al., Boston, United States. In Faseb J, 2012
GSTA4 down-regulation and the concomitant increase in 4-hydroxynonenal adducts in muscle are indicative of susceptibility to infection in individuals with severe thermal injuries.
Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease.
Raza, Ukraine. In Febs J, 2011
This review highlights the significance of the mitochondrial GST pool, particularly the mechanism and significance of dual targeting of GSTA4-4 under in vitro and in vivo conditions.
The balance between 4-hydroxynonenal and intrinsic glutathione/glutathione S-transferase A4 system may be critical for the epidermal growth factor receptor phosphorylation of human esophageal squamous cell carcinomas.
Shimosegawa et al., Sendai, Japan. In Mol Carcinog, 2011
Data show that mandatory overexpression of hGSTA4 by transient transfection in KYSE30 cells and attenuation of HNE-induced EGFR phosphorylation.
2-Aminoethoxydiphenyl borate administration into the nostril alleviates murine allergic rhinitis.
Zhao et al., Shanghai, China. In Am J Otolaryngol, 2011
2-APB treatment restrained nasal lavage fluid LTC4, ECP, ovalbumin-specific IgE, and IL-4 and their corresponding mRNAs in the previously mentioned tissues of treated mice in comparison with those of control ones.
Interactions of glutathione transferases with 4-hydroxynonenal.
Atkins et al., United States. In Drug Metab Rev, 2011
Some of the key determining characteristics that impart high alkenal activity reside in the unique C-terminal interactions of the GSTA4-4 enzyme.
Evidence that Gsta4 modifies susceptibility to skin tumor development in mice and humans.
DiGiovanni et al., United States. In J Natl Cancer Inst, 2010
Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans.
Novel mutations in leukotriene C4 synthase and risk of cardiovascular disease based on genotypes from 50,000 individuals.
Nordestgaard et al., Copenhagen, Denmark. In J Thromb Haemost, 2010
analysis of four novel mutations that change the function of leukotriene C(4) synthase and are associated with increased risk of venous thromboembolism and ischemic stroke
Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre.
Glei et al., Jena, Germany. In Mutat Res, 2009
In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced.
Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis.
El-Serag et al., Houston, United States. In Am J Epidemiol, 2008
Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively.
The use of glutathione transferase-knockout mice as pharmacological and toxicological models.
Board, Canberra, Australia. In Expert Opin Drug Metab Toxicol, 2007
So far, mice have been generated with deficiencies of mGSTP1/2, mGSTA4-4, mGSTZ1-1, mGSTM1-1, mGSTO1-1 and mGSTS1-1, but studies of drug metabolism in these strains have been limited.
Glutathione transferases.
Jowsey et al., Dundee, United Kingdom. In Annu Rev Pharmacol Toxicol, 2004
Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products.
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