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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
Increased 4-hydroxynonenal protein adducts in male GSTA4-4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease.
Petersen et al., Novara, Italy. In Am J Physiol Gastrointest Liver Physiol, 01 Apr 2015
To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male 129/SvJ mice (wild-type, WT) and glutathione S-transferase A4-4-null (GSTA4-/-) mice for 40 days.
The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes.
Singh et al., Lucknow, India. In Chem Biol Interact, 24 Mar 2015
While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glu tathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed.
Differential Proteomic Analysis of the Anti-depressive Effects of Oleamide in a Rat Chronic Mild Stress Model of Depression.
Wu et al., Shenyang, China. In Pharmacol Biochem Behav, 01 Mar 2015
CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1),acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4).
Reactive aldehyde-scavenging enzyme activities in atherosclerotic plaques of cigarette smokers and nonsmokers.
Cuccurullo et al., Chieti, Italy. In Atherosclerosis, 28 Feb 2015
METHODS: We have assessed specific enzymatic activities of class 1, 2, and 3 aldehyde dehydrogenase (ALDH1, ALDH2, and ALDH3, respectively), glutathione S-transferase (isozyme A4-4, GSTA4-4), and aldose reductase (AR), namely the major reactive aldehyde-scavenging enzymes, together with lipid peroxidation, i.e., fluorescent damage products of lipid peroxidation (FDPL), in carotid atherosclerotic plaques surgically removed from 17 cigarette smokers and 17 nonsmokers.
CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes.
Singh et al., Lucknow, India. In Mol Cell Biochem, Aug 2014
Cytochrome P4502E1 (CYP2E1), glutathione-S-transferase A4-4 (GSTA4-4), and inducible nitric oxide synthase (iNOS) are implicated in maneb- and paraquat-induced toxicity leading to various pathological conditions.
Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease.
Rahmani et al., Antibes, France. In Food Chem Toxicol, Aug 2014
However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway.
In vivo high-resolution magic angle spinning proton NMR spectroscopy of Drosophila melanogaster flies as a model system to investigate mitochondrial dysfunction in Drosophila GST2 mutants.
Tzika et al., Boston, United States. In Int J Mol Med, Jul 2014
Furthermore, direct links between GST2 mutation (the Drosophila ortholog of the GSTA4 gene in mammals) and insulin resistance, as suggested in this study, have not been made previously.
Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for Krüppel-like factor 4.
Hagos et al., New York City, United States. In Mol Carcinog, May 2014
Our RT-PCR result demonstrates that Klf4(-/-) MEFs have decreased expression of the antioxidant gene, Gsta4.
Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes.
Harashima et al., Sapporo, Japan. In Febs Open Bio, 2013
We found that the cellular reactive oxygen species (ROS) and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA) against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH), superoxide dismutase (SOD) and glutathione S-transferase A4 (GSTA4) were not altered.
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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