MISC

2008年10月

Novel function of glutathione transferase in rat liver mitochondrial membrane: Role for cytochrome c release from mitochondria

TOXICOLOGY AND APPLIED PHARMACOLOGY
  • Kang Kwang Lee
  • ,
  • Manami Shimoji
  • ,
  • Quazi Sohel Hossain
  • ,
  • Hajime Sunakawa
  • ,
  • Yoko Aniya

232
1
開始ページ
109
終了ページ
118
記述言語
英語
掲載種別
DOI
10.1016/j.taap.2008.06.005
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST-1. In the present Study, we aimed to determine whether mtMGST1 also Undergoes activation and about its function. When rats were treated with galactos galactosamine/lipopolysaccharide (GalN/LPS), mtMGST1 activity was significantly increased, and the increased activity was reduced by the disulfide reducing agent dithiothreitol. In mitochondria front GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed protein glutathione disulfides (glutathionylation) were detected. in addition, cytochrome c release front mitochondria isolated from GalN/LPS-treated rats was observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of mitochondria from control rats with diamide and diamide plus GSH in vitro resulted in dimer and mixed disulfide bond-mediated activation of mtMGST1, respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c release front the mitochondria, and the release was prevented by treatment with anti-MGST1 antibodies. In addition, diamide Plus GSH treatment Caused mitochondrial swelling accompanied by cytochrome c release, which was inhibited by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also inhibited by CsA and BKA. These results indicate that mtMGST1 is activated through mixed disulfide bond formation that contributes to cytochrome c release front mitochondria through the MPT pore. (C) 2008 Elsevier Inc. All rights reserved.


リンク情報
DOI
https://doi.org/10.1016/j.taap.2008.06.005
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000260134500012&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.taap.2008.06.005
  • ISSN : 0041-008X
  • eISSN : 1096-0333
  • Web of Science ID : WOS:000260134500012

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