Disease relevance of MGST2

• A novel MGST2 non-synonymous mutation in a Chinese pedigree with psoriasis vulgaris [1].
• Microsomal GST-III protein was expressed in a baculovirus insect cell system, and microsomes from Sf9 cells containing either microsomal GST-II or microsomal GST-III were both found to possess glutathione-dependent peroxidase activity as shown by their ability to reduce 5-HPETE to 5-HETE in the presence of reduced glutathione [2].

High impact information on MGST2

• Furthermore, Western blot analyses consistently demonstrated expression of LTC(4) synthase at the protein level in CML CD16(+) neutrophils, whereas expression of microsomal glutathione S-transferase 2 occurred occasionally [3].
• The apparent Km of 5-HPETE was determined to be approximately 7 microM for microsomal GST-II and 21 microM for microsomal GST-III [2].
• In this study, we investigated the physiological location of microsomal GST-II as well as the relative importance of this enzyme versus LTC4 synthase for the production of LTC4 in various human tissues and cells that have been previously demonstrated to possess LTC4 synthase activity [4].
• Based on the relative production of LTC4 to the LTC4 isomer, microsomal GST-II was demonstrated to be the principal enzyme responsible for LTC4 production in human liver microsomes and human endothelial cells and played a minor role in the formation of LTC4 in human lung membranes [4].
• Concomitant to the formation of LTC4, microsomal GST-II also produces a new metabolite of LTA4, a postulated LTC4 isomer [4].

Biological context of MGST2

• Unlike LTC4S, MGST2 prefers the naturally occurring free acid of LTA4 over the methyl ester as substrate and is also susceptible to product inhibition with an IC50 of about 1 microM for LTC4 [5].
• Microsomal GST-II has a wide tissue distribution (at the mRNA level) and was specifically expressed in human liver, spleen, skeletal muscle, heart, adrenals, pancreas, prostate, testis, fetal liver, and fetal spleen [6].
• We demonstrate that this mutation co-segregated with the disease phenotype within a Chinese family affected with psoriasis vulgaris and is predicted to have an impact on the normal function of MGST2 protein [1].
• Mapping of class alpha glutathione S-transferase 2 (GST-2) genes to the vicinity of the d locus on mouse chromosome 9 [7].
• Using a fibroblast cell line as a model, we have tested the effects of overexpression of three human GST (GSTA1, GSTP1, and MGSTII) on cell survival under a busulfan or melphalan challenge [8].

Anatomical context of MGST2

• Here, we report that MGST2, a distant homologue of LTC4S, is abundantly expressed in Human umbilical vein endothelial cells (HUVEC) and converts LTA4 into a single product, LTC4 [5].
• In contrast, microsomal GST-II mRNA expression was very low (when present) in lung, brain, placenta, and bone marrow [6].
• As determined by Western blot, microsomal GST-II was predominantly expressed in human liver microsomes, human endothelial cell membranes, and sparsely detected in human lung membranes [4].
• Like microsomal GST-II, microsomal GST-III has a wide tissue distribution (at the mRNA level) and is predominantly expressed in human heart, skeletal muscle, and adrenal cortex, and it is also found in brain, placenta, liver, and kidney tissues [2].

Associations of MGST2 with chemical compounds

• Thus, using Northern blot, RT-PCR, Western blot, and enzyme activity assays, we show that MGST2 is the main, if not the only, enzyme that converts LTA4 into LTC4 in membrane preparations of HUVEC [5].
• In addition, unlike LTC4 synthase, microsomal GST-II was able to catalyze the conjugation of 1-chloro-2, 4-dinitrobenzene with reduced glutathione [6].
• In an acute (24-hour) melphalan exposure assay, MGSTII conferred about a twofold selective advantage [8].
• In two separate assay formats using chronic exposure to busulfan, MGSTII conferred a reproducible twofold selective advantage [8].

Other interactions of MGST2

• Microsomal GST-II also catalyzed the formation of another product, displaying a conjugated triene UV absorption spectra with a maximum at 283 nm, suggesting less catalytic stereospecificity compared with LTC4 synthase [6].
• Microsomal GST-II also has a similar hydrophobicity pattern to FLAP, LTC4 synthase, and microsomal GST-I [6].
• Many of the identified genes (e.g., glutathione S-transferase [MGST2], thioredoxin reductase beta, and peroxiredoxin 2) have been identified as participants in OS responses in the lens and other systems [9].
• These data indicate that MGSTII may be a useful selective agent in hematopoietic gene therapy [8].

Analytical, diagnostic and therapeutic context of MGST2

• Fluorescent in situ hybridization mapped microsomal GST-II to chromosomal localization 4q28-31 [6].
• Here, we report the identification of a novel non-synonymous mutation in MGST2 by a comprehensive sequence analysis of MGST2's coding region in Chinese psoriasis samples [1].
• RTPCR analysis of human bone marrow CD34+ cells showed that MGSTII is not highly expressed in this stem/early progenitor population [8].

References