Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces cytochromes P450 (CYPs) such as CYP1A1 and CYP1A2 via activation of the aromatic hydrocarbon receptor (AHR). Herein we describe the TCDD-dependent enrichment of CYPs in liver microsomes and mitoplasts from C57BL/6J mice. TCDD-induced accumulation of CYP1A1 and CYP1A2 was observed in microsomes and mitoplasts after treatment with 15 microg TCDD/kg/d for 3d. While microsomal CYP1 proteins peaked at 1 week and diminished thereafter, mitoplast CYP1 proteins persisted 8 weeks at high levels. TCDD also induced microsomal CYP2A5, but not microsomal proteins immunoreactive to CYP2C11, CYP3A2 or CYP4A1 antibodies. Nevertheless, each of these proteins increased in mitoplasts following TCDD exposure. These results suggest that TCDD increases mitochondrial CYP immunoreactive proteins under the transcriptional control of the AHR, as well as CYPs that are not under AHR control. We speculate that such mitochondrial CYPs may be involved in the generation, or mitigation, of the well-known TCDD-inducible oxidative stress response.
Genter
Mary Beth
MB
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267-0056, USA.
Clay
Corey D
CD
Dalton
Timothy P
TP
Dong
Hongbin
H
Nebert
Daniel W
DW
Shertzer
Howard G
HG
D000818:Animals; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage*
D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2