title: Modulation of membrane-bound glutathione transferase activity by phospholipids including cardiolipin.
abstract: Membrane-bound glutathione transferases (MGST1) distributed mostly in liver microsomal and mitochondrial membranes are activated by the thiol modification. In the present study, the effect of phospholipids on MGST1 activity was investigated using purified enzyme. When MGST1 was mixed with liposomes of cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PC), or phosphatidylethanolamine (PE), its activity was increased in a magnitude which was dependent on the anionic property of lipids in the order of CL>PS>PE>PC, indicating that MGST1 activity is enhanced by surrounding anionic lipids. Although MGST1 was activated by the thiol alkylation with N-ethylmaleimide (NEM), the activation was suppressed in the presence of anionic phospholipids as clearly observed in the presence of CL. Similarly, the activation of MGST1 by diamide or diamide plus glutathione through disulfide-bond formation was also disturbed in the presence of CL. Suppression of NEM-derived MGST1 activation by CL was lost when MGST1 was incubated with CL in the presence of the detergent Triton X-100. These results indicate that reactivity (stability) of the thiol in MGST1 is affected by surrounding lipids, namely CL which prevents MGST1 activation by thiol modification. Since CL is a mitochondria specific lipid located in the inner membrane, it was suggested that function of mitochondrial MGST1 could be regulated by interaction with CL.
authors.affiliation: Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Shimoji
authors.forename: Naoki
authors.initials: N
authors.lastname: Imaizumi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aniya
mesh_terms: D000478:Alkylation; D000818:Animals; D000838:Anions / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D004220:Disulfides / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
chemical_list: D000838:Anions; D002308:Cardiolipins; D003902:Detergents; D004220:Disulfides; D008081:Liposomes; D010743:Phospholipids; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D003958:Diamide; D017830:Octoxynol; D005982:Glutathione Transferase; D005978:Glutathione; D005033:Ethylmaleimide