Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment
Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment
复制标题
DOI：
10.1016/j.bbrc.2006.02.121
复制
发表时间：
2006-04-21
影响因子：
3.1
通讯作者：
Shertzer, HG
中科院分区：
文献类型：
--
作者：
Genter, MB;Clay, CD;Shertzer, HG
TCDD（2,3,7,8-四氯二苯并-对二恶英）通过激活芳香烃受体（AHR）诱导细胞色素P450 （CYPs）如CYP1A1和CYP1A2。本研究描述了C57BL/6J小鼠肝微粒体和有丝质体中CYPs依赖于tcdd的富集。15 μ g TCDD/kg/d处理3天后，观察到微粒体和丝裂体中CYP1A1和CYP1A2的积累。微粒体CYP1蛋白在第1周达到峰值，随后下降，丝裂体CYP1蛋白持续8周处于高水平。TCDD也诱导微粒体CYP2A5，但对CYP2C11、CYP3A2或CYP4A1抗体没有免疫反应。然而，在TCDD暴露后，这些蛋白在有丝质体中均有所增加。这些结果表明，TCDD增加了线粒体在AHR转录控制下的CYP免疫反应蛋白，以及不受AHR转录控制的CYP。我们推测这些线粒体CYPs可能参与了众所周知的tcdd诱导的氧化应激反应的产生或缓解。(c) 2006爱思唯尔公司版权所有。
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 accumalation of CYP1A1 and CYP1A2 was observed in microsomes and mitoplasts after treatment with 15 mu g TCDD/kg/d for 3 d. 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. (c) 2006 Elsevier Inc. All rights reserved.