The distribution of microsomal glutathione transferase among different organelles, different organs, and different organisms

Morgenstern, Ralf; Lundqvist, Gerd; Andersson, Göran; Balk, Lennart; DePierre, Joseph W.

doi:10.1016/0006-2952(84)90145-x

Cited by 148 publications

(56 citation statements)

References 27 publications

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“…When the microsomal GST activity was expressed in µmol\min per mg of enzyme (assuming that 3.1 % of membrane protein is GST [14,20]), it was similar to that of cytosolic GSTs (16 versus 19 µmol\min per mg). When cysteine was used instead of GSH, neither microsomal nor cytosolic GSTs showed activity with CDNB.…”

Section: Activity With Different Thiolsmentioning

confidence: 99%

Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role of membrane-bound glutathione transferase

Akerboom

Sies

1996

Biochemical Journal

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The formation of S-nitrosoglutathione (GSNO) from amyl nitrite and n-butyl nitrite was studied in rat liver microsomes, employingN-ethylmaleimide (MalNEt) as an activator and indomethacin as an inhibitor of microsomal glutathione S-transferase (GST). Rates were compared with GST activity measured with 1-chloro-2,4-dinitrobenzene(CDNB) as a substrate. MalNEt stimulated GST activity and the formation of GSNO from amyl nitrite and n-butyl nitrite about 10-fold. Increasing concentrations of indomethacin inhibited both reactions in parallel. N-Acetyl-L-cysteine but not L-cysteine could substitute for GSH. It is concluded that rat liver microsomal GST catalyses the formation of GSNO from amyl nitrite and n-butyl nitrite. The activity of the MalNEt-stimulated microsomal GST is calculated to be about 17 units/mg of enzyme with the alkyl nitrites and about 16 units/mg of enzyme with CDNB as a substrate, assuming that 3% of microsomal protein is GST. These rates are comparable with those obtained for cytosolic GSTs. Thus microsomal GST may play a significant role in the metabolism of alkyl nitrites in biological membranes.

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Section: Activity With Different Thiolsmentioning

confidence: 99%

Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role of membrane-bound glutathione transferase

Akerboom

Sies

1996

Biochemical Journal

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“…14,15 Among the numerous cytosolic GST isozymes, the alpha-class displays the highest activity toward lipid hydroperoxides and has been implicated in the protection against oxidative stress. [16][17][18][19] The microsomal GST, different from the cytosolic family, comprise a family of small (16-to 18-kd), membrane-associated proteins that have been shown to be active as a trimer of identical subunits [20][21][22] ; its activity can be increased by treatment with N-ethylmaleimide and other sulphydryl reagents, heat, oxidative stress, and protein dimerization. 23,24 Microsomal GST is strongly expressed in liver and has a wide specificity for lipophilic and electrophilic substrates.…”

mentioning

confidence: 99%

Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress

2001

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Induction of cytochrome P450 2E1 (CYP2E1) and the formation of reactive oxygen species (ROS) appear to be one of the mechanisms by which ethanol is hepatotoxic. Glutathione peroxidase and catalase detoxify H 2 O 2 . Glutathione Stransferases (GST) provide protection from membrane lipid peroxidation, have GSH peroxidase activity, and reduce lipid hydroperoxides. Previous studies showed an up-regulation of GSH synthesis in CYP2E1 expressing HepG2 cells; this finding prompted an evaluation of the levels of other antioxidant exzymes. In CYP2E1 expressing cells, the alpha and microsomal GST messenger RNA (mRNA) are increased by 4-and 2-fold, respectively, and catalase protein and mRNA is increased by 2-fold. The increase in alpha and microsomal GST mRNA correlates with increased total enzymatic activity and is caused by increased transcription as evidenced by run-on transcription assays. In HepG2 cells transfected to express a different cytochrome P450, CYP3A4, there was an increase in alpha GST. However, in contrast to the CYP2E1 expressing cells, neither microsomal GST nor catalase were induced, suggesting some specificity for CYP2E1. In agreement with an increased antioxidant defense system, the sensitivity to added prooxidants such as menadione, antimycin A, H 2 O 2 , and 4-hydroxynonenal was lower in the CYP2E1 expressing cells as compared with control cells. In conclusion, overexpression of CYP2E1 in HepG2 cells, besides elevating total GSH levels, also induces expression of catalase and alpha and microsomal GST. This induction confers resistance to the cells against several prooxidants and is suggested to reflect an adaptive response by the cells against CYP2E1-mediated oxidative stress. (HEPATOLOGY 2001;33:652-661.)The glutathione S-transferases (GST; EC 2.5.1.18) are a family of enzymes that catalyze the conjugation of glutathione (GSH) to a wide variety of hydrophobic molecules of both exogenous and endogenous origin. 1-3 The cytosolic GSTs are dimeric proteins of subunits having a molecular mass in the 22-to 28-kd range. On the basis of their amino acid sequence, 5 classes have been described, namely alpha, mu, pi, theta, and sigma. [4][5][6] In humans the alpha class, subunits A1 and A2, is the predominant GST accounting for about 85% of the total GST protein. The major GST subunits expressed in rat liver are the alpha class, subunits A1 and A2, and the mu class, subunits 3 and 4, 7,8 whereas most of the cytosolic GST in HepG2 cells is the alpha isozyme. 9 ␣,␤, unsaturated aldehydes, such as 4-hydroxy-2,3-nonenal (4-HNE) and other endogenous or exogenous aldehydes, are generated in response to a variety of oxidative stimuli such as free intracellular iron, 10 chronic ethanol consumption, 11,12 and treatment with anticancer drugs. 13 GST-mediated conjugation of 4-HNE to GSH is the major pathway for 4-HNE metabolism. 14,15 Among the numerous cytosolic GST isozymes, the alpha-class displays the highest activity toward lipid hydroperoxides and has been implicated in the protection against oxidative stress. [1...

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“…The same or similar proteins, including cytochrome b 5 (cyt b 5 ; Refs. [3][4][5], NADH-cyt-b 5 reductase (6, 7), aldehyde dehydrogenase (8), glutathione Stransferase (9,10), and the proto-oncogene product Bcl-2 (11,12), are present in both membranes. To elucidate the mechanisms of the protein transport involving the development of the outer mitochondrial membrane, structural differences in targeting signals that direct proteins to each membrane system have to be defined.…”

mentioning

confidence: 99%

Charged Amino Acids at the Carboxyl-Terminal Portions Determine the Intracellular Locations of Two Isoforms of Cytochromeb 5

Kuroda

Ikenoue

Honsho

et al. 1998

Journal of Biological Chemistry

107

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Outer mitochondrial membrane cytochrome b 5 (OMb), which is an isoform of cytochrome b 5 (cyt b 5 ) in the endoplasmic reticulum, is a typical tail-anchored protein of the outer mitochondrial membrane. We cloned cDNA containing the complete amino acid sequence of OMb and found that the protein has no typical structural feature common to the mitochondrial targeting signal at the amino terminus. To identify the region responsible for the mitochondrial targeting of OMb, various mutated proteins were expressed in cultured mammalian cells, and the subcellular localization of the expressed proteins was analyzed. The deletion of more than 11 amino acid residues from the carboxyl-terminal end of OMb abolished the targeting of the protein to the mitochondria. When the carboxyl-terminal 10 amino acids of OMb were fused to the cyt b 5 that was previously deleted in the corresponding 10 residues, the fused protein localized in the mitochondria, thereby indicating that the carboxyl-terminal 10 amino acid residues of OMb have sufficient information to transport OMb to the mitochondria. The replacement of either of the two positively charged residues within the carboxyl-terminal 10 amino acids by alanine resulted in the transport of the mutant proteins to the endoplasmic reticulum. The mutant cyt b 5 , in which the acidic amino acid in its carboxyl-terminal end was replaced by basic amino acid, could be transported to the mitochondria. It would thus seem that charged amino acids in the carboxylterminal portion of these proteins determine their locations in the cell.

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The distribution of microsomal glutathione transferase among different organelles, different organs, and different organisms

Cited by 148 publications

References 27 publications

Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role of membrane-bound glutathione transferase

Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role of membrane-bound glutathione transferase

Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress

Charged Amino Acids at the Carboxyl-Terminal Portions Determine the Intracellular Locations of Two Isoforms of Cytochromeb 5

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