Genter Mary Beth, Clay Corey D, Dalton Timothy P, Dong Hongbin, Nebert Daniel W, Shertzer Howard G
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267-0056, USA.
Biochem Biophys Res Commun. 2006 Apr 21;342(4):1375-81. doi: 10.1016/j.bbrc.2006.02.121. Epub 2006 Feb 28.
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.
2,3,7,8-四氯二苯并对二噁英（TCDD）通过激活芳烃受体（AHR）诱导细胞色素P450（CYP）如CYP1A1和CYP1A2的产生。在此我们描述了C57BL/6J小鼠肝脏微粒体和线粒体中TCDD依赖性的CYP富集情况。在用15微克TCDD/千克/天处理3天后，在微粒体和线粒体中观察到TCDD诱导的CYP1A1和CYP1A2积累。虽然微粒体CYP1蛋白在1周时达到峰值，此后减少，但线粒体CYP1蛋白在8周内持续保持高水平。TCDD还诱导了微粒体CYP2A5，但未诱导与CYP2C11、CYP3A2或CYP4A1抗体发生免疫反应的微粒体蛋白。然而，在TCDD暴露后，这些蛋白在每个线粒体中均增加。这些结果表明，TCDD在AHR的转录控制下增加线粒体CYP免疫反应蛋白，以及不受AHR控制的CYP。我们推测，这种线粒体CYP可能参与了众所周知的TCDD诱导的氧化应激反应的产生或减轻。
