Nuclear and nucleolar glutathione reductase, peroxidase, and transferase activities in livers of male and female Fischer-344 rats.
The present studies were to test the hypotheses that glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities are expressed in nuclei and nucleoli of rat liver cells, and that differences in activities of these enzymes would correlate with the greater resistance of female than of male Fischer-344 rats to hepatic necrosis in vivo, mediated by reactive oxygen species generated by redox-cycling metabolism of diquat. Adult male and female Fischer-344 rats were treated with comparably hepatotoxic doses of diquat (0.1 or 0.2 mmol/kg, respectively), or equal volumes of saline, ip. Six hours later, the livers were harvested, and purified nuclei and nucleoli were isolated by differential centrifugation. Nuclear GR activities in male and female rats were 12 and 15 mU/mg protein, and nucleolar activities were 30 and 51 mU/mg protein, respectively, p < 0.05. Some differences between male and female rats in nuclear and nucleolar activities of GPXs and GSTs were observed, as were some differences in the respective diquat-treated animals, but implications of these differences for susceptibility to diquat-induced oxidant stress effects are not apparent. Nuclear GR, GPX, and GST probably contribute to antioxidant defense mechanisms, but the functions served by localization of GR and GPX in nucleoli are less evident.
Rogers
Lynette K
LK
Children's Research Institute, Center for Developmental Pharmacology and Toxicology, and Department of Pediatrics, Children's Hospital, The Ohio State University, Columbus, Ohio 43205, USA. rogersl@chi.osu.edu
Gupta
Sanjiv
S
Welty
Stephen E
SE
Hansen
Thomas N
TN
Smith
Charles V
CV
D000818:Animals; D015153:Blotting, Western; D002466:Cell Nucleolus / Q000201:enzymology*; D002467:Cell Nucleus / Q000201:enzymology*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology; D004247:DNA / Q000378:metabolism; D004178:Diquat / Q000633:toxicity; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism
D006540:Herbicides; D017382:Reactive Oxygen Species; D004247:DNA; D004178:Diquat; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase