Effects of glutathione reductase inhibition on cellular thiol redox state and related systems.
Although inhibition of glutathione reductase (GR) has been demonstrated to cause a decrease in reduced glutathione (GSH) and increase in glutathione disulfide (GSSG), a systematic study of the effects of GR inhibition on thiol redox state and related systems has not been noted. By employing a monkey kidney cell line as the cell model and 2-acetylamino-3-[4-(2-acetylamino-2-carboxy-ethylsulfanylthio carbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a GR inhibitor, an investigation of the effects of GR inhibition on cellular thiol redox state and related systems was conducted. Our study demonstrated that, in addition to a decrease in GSH and increase in GSSG, 2-AAPA increased the ratios of NADH/NAD(+) and NADPH/NADP(+). Significant protein glutathionylation was observed. However, the inhibition did not affect the formation of reactive oxygen species or expression of antioxidant defense enzyme systems [GR, glutathione peroxidase, catalase, and superoxide dismutase] and enzymes involved in GSH biosynthesis [gamma-glutamylcysteine synthetase and glutathione synthetase].
Zhao
Yong
Y
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Seefeldt
Teresa
T
Chen
Wei
W
Wang
Xiuqing
X
Matthees
Duane
D
Hu
Yueshan
Y
Guan
Xiangming
X
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D004220:Disulfides / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019803:Glutathione Disulfide / Q000096:biosynthesis / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology*
C539612:2-acetylamino-3-(4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl)propionic acid; D000975:Antioxidants; D004220:Disulfides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D009243:NAD; D009249:NADP; D005980:Glutathione Reductase; D019803:Glutathione Disulfide; D000111:Acetylcysteine