3,3',4,4',5-Pentachlorobiphenyl (PCB 126) impacts hepatic lipid peroxidation, membrane fluidity and beta-adrenoceptor kinetics in chick embryos.
Polychlorinated biphenyls (PCB) and other aryl hydrocarbon receptor (AHR) agonists induce oxidative stress and alter membrane lipid peroxidation and fluidity. This study tested the hypothesis that PCB-induced changes in membrane properties impact membrane beta-adrenoceptor (beta-AR) affinity and capacity in chick embryo hepatocytes. Embryos were injected into the air cell with 1.6 microg 3,3',4,4',5-pentachlorobiphenyl (PCB 126)/kg egg at day 0, and incubated to day 19 when livers were removed. This dose resulted in hepatic PCB 126 levels of 0.67 ng/g liver or 10.2 ng/g liver lipid; levels in untreated embryos were non-detectable. Hepatic microsomal EROD activity was elevated by approximately 12-fold and embryo mortality was significantly increased compared with the untreated group. Hepatic lipid peroxidation increased and membrane order (steady-state fluorescence anisotropy values) decreased with in ovo PCB 126 exposure. Consistent with changes in membrane structure, hepatic beta-AR affinity for CGP 12177 significantly decreased (Kd increased) without changes in receptor numbers. This study demonstrates that in ovo exposure to PCB 126 in chick eggs significantly impacted embryo survival, and this was correlated with altered hepatic membrane structure and ultimately membrane function.
Department of Biology, University of Ottawa, 150 Louis Pasteur, Ottawa, ON, Canada K1N 6N5.
A L
AL
Katynski
M M
MM
Vijayan
S W
SW
Kennedy
T W
TW
Moon
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo / Q000187:drug effects* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005454:Fluorescence Polarization; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D008862:Microsomes, Liver / Q000201:enzymology; D010063:Ovum / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C033394:CGP 12177; C023035:3,4,5,3',4'-pentachlorobiphenyl; D017265:Procaterol; D004837:Epinephrine