Effects of Hypoxia Exposure on Hepatic Cytochrome P450 1A (CYP1A) Expression in Atlantic Croaker: Molecular Mechanisms of CYP1A Down-Regulation

dc.creatorRahman, Md. Sayduren
dc.creatorThomas, Peteren
dc.date.accessioned2013-05-23T15:53:49Zen
dc.date.available2013-05-23T15:53:49Zen
dc.date.issued2012-07-16en
dc.description.abstractHypoxia-inducible factor-α (HIF-α) and cytochrome P450 1A (CYP1A) are biomarkers of environmental exposure to hypoxia and organic xenobiotic chemicals that act through the aryl hydrocarbon receptor, respectively. Many aquatic environments heavily contaminated with organic chemicals, such as harbors, are also hypoxic. Recently, we and other scientists reported HIF-α genes are upregulated by hypoxia exposure in aquatic organisms, but the molecular mechanisms of hypoxia regulation of CYP1A expression have not been investigated in teleost fishes. As a first step in understanding the molecular mechanisms of hypoxia modulation of CYP1A expression in fish, we characterized CYP1A cDNA from croaker liver. Hypoxia exposure (dissolved oxygen, DO: 1.7 mg/L for 2 to 4 weeks) caused significant decreases in hepatic CYP1A mRNA and protein levels compared to CYP1A levels in fish held in normoxic conditions. In vivo studies showed that the nitric oxide (NO)-donor, S-nitroso-N-acetyl-DL-penicillamine, significantly decreased CYP1A expression in croaker livers, whereas the competitive inhibitor of NO synthase (NOS), Nω-nitro-L-arginine methyl ester, restored CYP1A mRNA and protein levels in hypoxia-exposed (1.7 mg DO/L for 4 weeks) fish. In vivo hypoxia exposure also markedly increased interleukin-1β (IL-1β, a cytokine), HIF-2α mRNA and endothelial NOS (eNOS) protein levels in croaker livers. Pharmacological treatment with vitamin E, an antioxidant, lowered the IL-1β, HIF-2α mRNA and eNOS protein levels in hypoxia-exposed fish and completely reversed the down-regulation of hepatic CYP1A mRNA and protein levels in response to hypoxia exposure. These results suggest that hypoxia-induced down-regulation of CYP1A is due to alterations of NO and oxidant status, and cellular IL-1β and HIF-α levels. Moreover, the present study provides the first evidence of a role for antioxidants in hepatic eNOS and IL-1β regulation in aquatic vertebrates during hypoxic stress.en
dc.description.departmentMarine Scienceen
dc.description.sponsorshipThis study was supported by a grant from the National Oceanic and Atmospheric Administration Coastal Ocean Program Gulf of Mexico GOMEX, grant no. NA09NOS4780179 to PT, publication no. NGOMEX 1**, and National Science Foundation, grant no. IOS-1119242 to PT. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationRahman MS, Thomas P (2012) Effects of Hypoxia Exposure on Hepatic Cytochrome P450 1A (CYP1A) Expression in Atlantic Croaker: Molecular Mechanisms of CYP1A Down-Regulation. PLoS ONE 7(7): e40825. doi:10.1371/journal.pone.0040825en
dc.identifier.doi10.1371/journal.pone.0040825en
dc.identifier.urihttp://hdl.handle.net/2152/20146en
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.rightsAttribution 3.0 United Statesen
dc.rightsCC-BYen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en
dc.subjectAntioxidantsen
dc.subjectComplementary DNAen
dc.subjectDissolved oxygenen
dc.subjectFishesen
dc.subjectMedical hypoxiaen
dc.subjectNitric oxideen
dc.subjectProtein expressionen
dc.subjectVitamin Een
dc.titleEffects of Hypoxia Exposure on Hepatic Cytochrome P450 1A (CYP1A) Expression in Atlantic Croaker: Molecular Mechanisms of CYP1A Down-Regulationen
dc.typeArticleen

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