Induction of the nuclear factor HIF-1alpha in acetaminophen toxicity: evidence for oxidative stress
- PMID: 16530163
- DOI: 10.1016/j.bbrc.2006.02.143
Induction of the nuclear factor HIF-1alpha in acetaminophen toxicity: evidence for oxidative stress
Abstract
Hypoxia inducible factor (HIF) controls the transcription of genes involved in angiogenesis, erythropoiesis, glycolysis, and cell survival. HIF-1alpha levels are a critical determinant of HIF activity. The induction of HIF-1alpha was examined in the livers of mice treated with a toxic dose of APAP (300 mg/kg i.p.) and sacrificed at 1, 2, 4, 8, and 12 h. HIF-1alpha 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 i.p.) prevented toxicity and HIF-1alpha induction. In further studies, hepatocyte suspensions were incubated with APAP (1 mM) in the presence of an oxygen atmosphere. HIF-1alpha was induced at 1 h, prior to the onset of toxicity. Inclusion of cyclosporine A (10 microM), an inhibitor of mitochondrial permeability transition, oxidative stress, and toxicity, prevented the induction of HIF-1alpha. Thus, HIF-1alpha 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-1alpha in APAP toxicity.
Similar articles
-
Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice.Toxicol Appl Pharmacol. 2012 Oct 15;264(2):192-201. doi: 10.1016/j.taap.2012.08.001. Epub 2012 Aug 10. Toxicol Appl Pharmacol. 2012. PMID: 22902588 Free PMC article.
-
Acetaminophen hepatotoxicity and HIF-1α induction in acetaminophen toxicity in mice occurs without hypoxia.Toxicol Appl Pharmacol. 2011 May 1;252(3):211-20. doi: 10.1016/j.taap.2011.02.005. Epub 2011 Feb 24. Toxicol Appl Pharmacol. 2011. PMID: 21316383 Free PMC article.
-
Cellular redox status regulates hypoxia inducible factor-1 activity. Role in tumour development.J Exp Clin Cancer Res. 2007 Mar;26(1):39-50. J Exp Clin Cancer Res. 2007. PMID: 17550131 Review.
-
Hypoxia-inducible factor-1 (HIF-1).Mol Pharmacol. 2006 Nov;70(5):1469-80. doi: 10.1124/mol.106.027029. Epub 2006 Aug 3. Mol Pharmacol. 2006. PMID: 16887934 Review.
-
Hyperbaric oxygen reduces acetaminophen toxicity and increases HIF-1alpha expression.Acad Emerg Med. 2006 Jul;13(7):707-14. doi: 10.1197/j.aem.2006.01.029. Epub 2006 Apr 24. Acad Emerg Med. 2006. PMID: 16636360
Cited by
-
Hypoxia-induced factor and its role in liver fibrosis.PeerJ. 2022 Dec 6;10:e14299. doi: 10.7717/peerj.14299. eCollection 2022. PeerJ. 2022. PMID: 36523459 Free PMC article. Review.
-
In Silico Exploration of the Potential Role of Acetaminophen and Pesticides in the Etiology of Autism Spectrum Disorder.Toxics. 2021 Apr 27;9(5):97. doi: 10.3390/toxics9050097. Toxics. 2021. PMID: 33925648 Free PMC article.
-
Hypoxia-Inducible Factor-2α Reprograms Liver Macrophages to Protect Against Acute Liver Injury Through the Production of Interleukin-6.Hepatology. 2020 Jun;71(6):2105-2117. doi: 10.1002/hep.30954. Epub 2020 Feb 4. Hepatology. 2020. PMID: 31529728 Free PMC article.
-
Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice.Lipids Health Dis. 2017 Aug 14;16(1):153. doi: 10.1186/s12944-017-0540-4. Lipids Health Dis. 2017. PMID: 28807032 Free PMC article.
-
Role of Hypoxia-Inducible Factors in the Development of Liver Fibrosis.Cell Mol Gastroenterol Hepatol. 2015 Sep 25;1(6):589-597. doi: 10.1016/j.jcmgh.2015.09.005. eCollection 2015 Nov. Cell Mol Gastroenterol Hepatol. 2015. PMID: 28210703 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
