Disease relevance of MGST1

• Rat basophilic leukemia cells and murine mastocytoma cells, two well-known sources of leukotriene C synthase, both expressed microsomal glutathione S-transferase as determined by Western blot analyses [1].
• These results indicate that the enzyme responsible for the conversion of LTA4 to LTC4 in human melanoma cells is LTC4 synthase rather than a nonspecific or microsomal glutathione-S-transferase [2].

High impact information on MGST1

• The 3D structure differs significantly from that of soluble glutathione transferases, which display overlapping substrate specificity with MGST1 [3].
• Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress [4].
• In this respect, MGST1 is similar to glutathione peroxidases that also transcriptionally respond to oxidative stress [5].
• The MGST1 gene has two alternative first exons and is located in the 12p13.1-13.2 region [5].
• Structural organization of the microsomal glutathione S-transferase gene (MGST1) on chromosome 12p13.1-13.2. Identification of the correct promoter region and demonstration of transcriptional regulation in response to oxidative stress [5].

Biological context of MGST1

• Microsomal GST-I: genomic organization, expression, and alternative splicing of the human gene [6].
• Catalog of 46 single-nucleotide polymorphisms (SNPs) in the microsomal glutathione S-transferase 1 (MGST1) gene [7].
• Among the 13 insertion-deletion polymorphisms was a 2-bp deletion in the coding region of MGST1 in DNA from one of the volunteers, which resulted in a frame-shift mutation [7].
• Using the cDNA as the hybridization probe, we now report the assignment of the human microsomal GST gene to chromosome 12 through the use of a panel of mouse-human somatic cell hybrid lines [8].
• The gene for the microsomal glutathione S-transferase is on human chromosome 12 [8].

Anatomical context of MGST1

• Human umbilical vein endothelial cells generate leukotriene C4 via microsomal glutathione S-transferase type 2 and express the CysLT(1) receptor [9].
• In aortic microsomes from GTN-tolerant animals, there was a decreased abundance of MGST1 dimers and trimers [10].
• Besides, only MGST1 localized on endoplasmic reticulum (ER), but not mitochondria which favors protein S-nitrosylation was examined in the previous report [11].
• In hepatocytes, neither ER nor mitochondria were found to contain S-nitrosylated MGST1 after GSNO treatment, showing that differently distributed MGST1 was consistently un-nitrosylable in the cellular environment [11].
• Microsomal glutathione S-transferase is the predominant leukotriene C4 binding site in cellular membranes [12].

Associations of MGST1 with chemical compounds

• This tyrosine is not conserved in MGST1 or MGST1-L1 [13].
• Microsomal glutathione transferase (MGST1) and prostaglandin E synthase (PGES) are both members of the MAPEG (Membrane Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily [14].
• Alkylation of the sole cysteine residue of MGST1 by N-ethylmaleimide markedly increased enzyme activity with CDNB as substrate but decreased the rate of GTN denitration [10].
• Both oxidants and nitrating reagents increased the activity of MGST1 toward the GST substrate, 1-chloro-2,4-dinitrobenzene (CDNB) whereas these treatments inhibited GTN denitration by MGST1 [10].
• Although the biotransformation of organic nitrates by the cytosolic glutathione S-transferases (GSTs) is well known, the relative contribution of the microsomal GST (MGST1) to nitrate biotransformation has not been described [10].

Other interactions of MGST1

• Therefore, it is proposed that this novel membrane protein is a member of the microsomal glutathione S-transferase family, also including LTC4 synthase, with significant sequence identities to both LTC4 synthase and FLAP [15].
• The present work describes the identification and characterization of a novel member of this family termed microsomal glutathione S-transferase III (microsomal GST-III) [16].
• Microsomal GST-II also has a similar hydrophobicity pattern to FLAP, LTC4 synthase, and microsomal GST-I [15].
• We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls [17].
• Microsomal glutathione S-transferase was immobilized on NHS-activated Sepharose 4B and used as an affinity matrix [18].

Analytical, diagnostic and therapeutic context of MGST1

• In addition, genomic Southern blotting data suggest that the human microsomal GST is encoded by a single- or very-low-copy gene [8].
• Here we propose that this superfamily consists of a new class of membrane proteins built on a common left-handed four-helix bundle motif within the membrane, as determined by electron crystallography of MGST1 at 6 A resolution [3].
• Colocalization of leukotriene C synthase and microsomal glutathione S-transferase elucidated by indirect immunofluorescence analysis [1].
• We have studied the distribution of four isoenzymes, acidic, basic, neutral, and microsomal GST in human liver, gall bladder, and small and large intestinal epithelium by immunohistochemistry [19].
• Expression of NQO-1, GST-alpha, gamma-glutamylcysteine synthetase-heavy and -light chains, and microsomal GST was assessed by Northern blot analysis [20].

References