Prior PCB exposure suppresses hypoxia-induced up-regulation of glycolytic enzymes in Fundulus heteroclitus.
Increased activity of the glycolytic enzymes is a conserved feature of the cellular response to hypoxia, and may represent a protective mechanism by which cells can survive short-term hypoxic exposure. Gene induction by hypoxia involves a dimer of the hypoxia inducible factor (HIF)-1 alpha and the nuclear cofactor HIF-1 beta, also called the aryl hydrocarbon receptor nuclear translocator (ARNT), which is also involved in induction of genes in response to aryl hydrocarbon exposure. To assess the possibility of interaction between these pathways, we examined changes in the activity of the glycolytic enzymes in response to hypoxia and polychlorinated biphenyl (PCB) exposure in the liver of a teleost fish, Fundulus heteroclitus. After 3 days of hypoxic exposure (dissolved oxygen levels between 1.5 and 2.0 mg/L), there were significant increases in the activity of six glycolytic enzymes (PGI, ALD, TPI, PGK, PGM and LDH). In contrast, intraperitoneal injection of 1 microg/g body weight of PCB #77 (3,3',4,4'-tetrachlorobiphenyl) caused significant decreases in glycolytic enzyme activity after 7 days of exposure. When fish were injected with PCB #77 and then (4 days later) exposed to hypoxia for 3 days as before, we observed no induction of the glycolytic enzymes. This suggests that there is an antagonistic interaction between exposure to PCBs and hypoxia in F. heteroclitus. Prior PCB exposure could make these fish less tolerant of environmental hypoxia.
Kraemer
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INRS-ETE, Université du Québec, C.P. 7500, Sainte Foy, QC, Canada.
Schulte
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015687:Cell Hypoxia; D004790:Enzyme Induction / Q000187:drug effects; D023781:Fundulidae / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006019:Glycolysis; D007274:Injections, Intraperitoneal; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation; D015854:Up-Regulation
D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl