Disease relevance of Gsta4

• In conclusion, the present study provides evidence for the occurrence of GST A4-4 enzyme activity in mammalian mitochondria, in addition to demonstrating that both mitochondria and microsomes are intracellular targets for nicotine- and NNK-induced organ toxicity [1].

Psychiatry related information on Gsta4

• Alterations in GSH and other GSH-related enzymes at 3 and 10 days support the concept that--upon AA exposure--aortic defense mechanisms respond early and induction of GSH biosynthesis and rat GST8-8 occur to alleviate the toxic effects of acrolein, a major, genotoxic product of AA metabolism [2].

High impact information on Gsta4

• All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels [3].
• Transient transfection of COS cells with CYP2E1 cDNA caused a similar accumulation of CYP2E1 and GST A4-4 in mitochondria and increased production of mitochondrial ROS [4].
• These studies suggest that mouse GST 5.7 structurally corresponds to rat GST 8-8 and belongs to the Alpha class [5].
• In general, GST 7-7 was better than GST 8-8 in utilizing these analogues as substrates, and glycyl analogues were better than gamma-glutamyl analogues as both substrates and inhibitors [6].
• The 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-induced oxidative damage was apparent in the microsomal fraction of brain, lung, and liver, and it also increased 4-hydroxynonenal specific GST A4-4 activity in the brain and lung mitochondrial matrix fraction [1].

Biological context of Gsta4

• We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3 [7].
• Gsta4 expression was strongly correlated with the gene dose of var3, with approximately 60% of the variance in expression accounted for by genotype at this locus [7].
• The presence of GST8-8 in the vasculature, which is constantly exposed to products of lipid peroxidation, and its induction by AA, suggest that GST8-8 plays a key role in protecting blood vessels against oxidative stress and hence, may be involved in the atherogenic process [2].

Anatomical context of Gsta4

• Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the gravid uterus [8].
• By immunohistochemistry, GST8-8 was localized in the smooth muscle cells of the vascular media which is believed to be the site of metabolism of AA [2].
• Rat GST 8-8 was highly expressed in hippocampus, the choroid plexus of the dorsal third ventricle and the lateral ventricle, and ependymal cells along the dorsal third ventricle and the third ventricle [9].
• Additionally, immunoblots demonstrated that Kupffer cells contain ALDH 1 and ALDH 2 isoforms as well as GST A4-4, P1-1, Ya, and Yb [10].
• Immunohistochemical studies show that BHT induced GST8-8 several folds in the epithelium [11].

Associations of Gsta4 with chemical compounds

• Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated approximately 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats [7].
• Acceptor substrates for GST 7-7 were 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (ETA) and for GST 8-8 CDNB, ETA and 4-hydroxynon-trans-2-enal (HNE) [6].

Analytical, diagnostic and therapeutic context of Gsta4

• Western blot of purified total GSTs using antibodies against rec-mGSTA4-4 revealed a single band at 25 kDa, confirming the presence of a GST isozyme immunologically similar to rat GST8-8, which is known to utilize alpha,beta-unsaturated carbonyls as preferred substrates [12].

References