Home > Explore Data & Reports > Effects of hypoxia exposure on hepatic cytochrome P450 1A (CYP1A) expression in Atlantic croaker: molecular mechanisms of CYP1A down-regulation

Citation:

Rahman, Md.S., and P. Thomas. 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):1-14. https://doi.org/10.1371/journal.pone.0040825

Data/Report Type:

Sponsored Research

Description

Hypoxia-inducible factor-? (HIF-?) 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-? 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), N?-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-1? (IL-1?, a cytokine), HIF-2? mRNA and endothelial NOS (eNOS) protein levels in croaker livers. Pharmacological treatment with vitamin E, an antioxidant, lowered the IL-1?, HIF-2? 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-1? and HIF-? levels. Moreover, the present study provides the first evidence of a role for antioxidants in hepatic eNOS and IL-1? regulation in aquatic vertebrates during hypoxic stress.

Note to readers with disabilities: Some scientific publications linked from this website may not conform to Section 508 accessibility standards due to the complexity of the information being presented. If you need assistance accessing this electronic content, please contact the lead/corresponding author, Primary Contact, or nccos.webcontent@noaa.gov.

Explore Similar Data/Reports

About NCCOS

NCCOS delivers ecosystem science solutions for stewardship of the nation’s ocean and coastal resources to sustain thriving coastal communities and economies.

Stay Connected

Sign up for our quarterly newsletter or view our archives.

Follow us on Social

Listen to our Podcast

Check our our new podcast "Coastal Conversations"