Induction of the nuclear factor HIF-1{alpha} in acetaminophen toxicity: Evidence for oxidative stress
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States) and Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (United States) and Arkansas Children's Hospital Research Institute, Little Rock, AR (United States)
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (United States)
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States)
Hypoxia inducible factor (HIF) controls the transcription of genes involved in angiogenesis, erythropoiesis, glycolysis, and cell survival. HIF-1{alpha} levels are a critical determinant of HIF activity. The induction of HIF-1{alpha} was examined in the livers of mice treated with a toxic dose of APAP (300 mg/kg IP) and sacrificed at 1, 2, 4, 8, and 12 h. HIF-1{alpha} was induced at 1-12 h and induction occurred prior to the onset of toxicity. Pre-treatment of mice with N-acetylcysteine (1200 mg/kg IP) prevented toxicity and HIF-1{alpha} induction. In further studies, hepatocyte suspensions were incubated with APAP (1 mM) in the presence of an oxygen atmosphere. HIF-1{alpha} was induced at 1 h, prior to the onset of toxicity. Inclusion of cyclosporine A (10 {mu}M), an inhibitor of mitochondrial permeability transition, oxidative stress, and toxicity, prevented the induction of HIF-1{alpha}. Thus, HIF-1{alpha} is induced before APAP toxicity and can occur under non-hypoxic conditions. The data suggest a role for oxidative stress in the induction of HIF-1{alpha} in APAP toxicity.
- OSTI ID:
- 20798921
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 343, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.02.143; PII: S0006-291X(06)00452-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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