Disease relevance of GSTO1

• Recently an association of Glutathione S-Transferase Omega 1 (GSTO1) and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD) and Parkinson's disease (PD) [1].
• In this case control study, 28 cases of hepatocellular carcinoma, 30 cases of cholangiocarcinoma, 31 cases of colorectal cancer, 30 cases of breast cancer and 98 controls were compared for frequencies of GSTO1 and GSTO2 genotypes [2].
• In situ analysis located the papillomas Glutathione S-transferase omega 1 expression to the proliferating areas of the papillomas [3].
• Retrovirus expressing a dominant negative FGFR construct (FGFRdn) and green fluorescent protein (GFP) was injected into the dorsal columns of postnatal day 7 (P7) mice followed by perfusion at P28 [4].
• A high degree of correlation in values of ELISAs based on P28 and on the phenolic glycolipid of Mycobacterium leprae was observed in all groups analyzed [5].

Psychiatry related information on GSTO1

• Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease [6].
• BACKGROUND: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke [7].
• Glutathione S-Transferase Omega 1 variation does not influence age at onset of Huntington's disease [1].

High impact information on GSTO1

• The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta [8].
• Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor [8].
• Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease [8].
• Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD [9].
• We subjected male Sprague-Dawley rats at postnatal day (P)7, P14, P21, and P28 to either a saline or lipopolysaccharide (LPS) injection and examined them in adulthood for differences in responses to a further LPS injection [10].

Chemical compound and disease context of GSTO1

• Mice (BALB/c) were vaccinated with the HIV-1 gp120 envelope glycoprotein (Env(gp120)) alone or fused to multiple copies of the murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2 binding domain [11].

Biological context of GSTO1

• Both GSTO1 and GSTO2 are composed of six exons and are separated by 7.5 kb on chromosome 10q24 [12].
• GSTO2 has 64% amino acid identity with GSTO1 and conserves the cysteine residue at position 32, which is thought to be important in the active site of GSTO1 [12].
• Glutathione S-transferase omega 1 and omega 2 (GSTO1 and GSTO2) catalyze monomethyl arsenate reduction, the rate-limiting reaction in arsenic biotransformation [13].
• We identified 31 and 66 polymorphisms in GSTO1 and GSTO2, respectively, with four nonsynonymous-coding single nucleotide polymorphisms (cSNPs) in each gene [13].
• Quantitative Western blot analysis, after correction for transfection efficiency, showed a reduction in protein level of greater than 50% for the GSTO1 Tyr32 variant allozyme compared with wild type (WT), whereas levels for the Asp140, Lys208, Val236, and codon 155 deletion variant constructs were similar to that of the WT [13].

Anatomical context of GSTO1

• Expression constructs were created for all eight nonsynonymous cSNPs, as well as a deletion of codon 155 in GSTO1, and those constructs were used to transfect COS-1 cells [13].
• Rabbit reticulocyte lysate degradation studies showed that the GSTO1 Tyr32 and the GSTO2 Tyr130, Ile158, and Asp142/Ile158 variant allozymes were degraded more rapidly than were their respective WT allozymes [13].
• We conclude that GSTO1 variants do not influence the risk for thyroid nodules or their pathologic and clinical characteristics [14].
• After the neonatal production of CRE and the initiation of KIF3A loss, ectopic accumulation of opsin was detected by postnatal day (P)7, and ensuing photoreceptor cell death was evident after P10 and almost complete by P28 [15].
• In contrast, a strong signal was apparent in the anterodorsal nucleus, which projects to limbic areas, and this persisted at P28 [16].

Associations of GSTO1 with chemical compounds

• A genetic polymorphism of the GSTO1 gene causing an alanine-to-aspartate (A140D) substitution in amino acid 140 produces a variant with lowered enzyme activities in the biotransformation of inorganic arsenic, a common contaminant of drinking water in many regions of the world and a well-known carcinogen [14].
• GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05) [7].
• CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype [7].
• Glutathione-S-transferase class Omega (GSTO 1-1) belongs to a new subfamily of GSTs, which is identical with human monomethylarsonic acid (MMA(V)) reductase, the rate limiting enzyme for biotransformation of inorganic arsenic, environmental carcinogen [17].
• No significant difference was observed in GST activity towards 1-chloro-2,4-dinitrobenzene, whereas thioltransferase activity was decreased to 75% (Ala140Asp) and 40% (Thr217Asn) of the wild-type GSTO 1-1 [17].

Other interactions of GSTO1

• Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans [18].
• CONCLUSION: The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies [7].
• We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb [19].

Analytical, diagnostic and therapeutic context of GSTO1

• The livers of male knockout (KO) mice, in which 222 bp of Exon 3 of the GSTO1 gene were eliminated, were analyzed by PCR for mRNA [20].
• Extensive immunohistochemistry of rat and human tissue sections has demonstrated cellular and subcellular specificity in the expression of GSTO1-1 [21].
• Sequence alignments showed that CLIC-2 has a high degree of sequence similarity with CLIC-1 and some similarity to the omega class of glutathione transferases (GSTO) [22].
• Methods: Organ of Corti explants and dissociated spiral ganglion cell cultures obtained from 3-day-old (P3) rats or adult spiral ganglion cell cultures from 28-day-old (P28) rats were transduced with vectors containing a human bcl-2 gene [23].
• The fusion of C3d or P28 to Env(gp120) elicited higher-titer anti-Env specific antibody, enhanced avidity maturation of the elicited antibody, and elicited higher numbers of IFN-gamma and IL-4 secreting cells compared to Env(gp120) immunizations [11].

References