Expression profile of cytochrome P450s and effects of polycyclic aromatic hydrocarbons and antiepileptic drugs on CYP1 expression in MOG-G-CCM cells
Expression profile of cytochrome P450s and effects of polycyclic aromatic hydrocarbons and antiepileptic drugs on CYP1 expression in MOG-G-CCM cells
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MOG-G-CCM细胞中细胞色素P450的表达谱以及多环芳烃和抗癫痫药物对CYP1表达的影响
DOI：
10.1016/j.lfs.2020.118140
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Shigeru Ohmori
中科院分区：
文献类型：
--
作者：
Shusuke Ozawa;Satoshi Yamaori;Kaori Aikawa;Shinobu Kamijo;Shigeru Ohmori
本研究采用实时荧光定量PCR、Western blotting和免疫细胞化学等方法，观察细胞色素P450（CYP 450）亚型在人星形细胞瘤MOG-G-CCM细胞中的表达，并探讨多环芳烃（PAHs）和抗癫痫药物对MOG-G-CCM细胞CYP 1表达的影响。在分析的CYP 1B 1亚型中，CYP 1B 1的表达水平最高，其次是CYP 1A 1。此外，CYP 1B 1定位于内质网和线粒体中。3-甲基胆蒽（3-MC）、苯并[a]蒽（B[a]A）、苯并[a]芘（B[a]P）和丙戊酸（VPA）可增加CYP 1B 1和CYP 1A 1的表达。强效芳烃受体拮抗剂GNF 351显著抑制3-MC和VPA介导的CYP 1B 1和CYP 1A 1上调。此外，VPA可增强3-MC、B[a]A和B[a]P对CYP 1B 1和CYP 1A 1的诱导作用，但对CYP 1A 1的增强作用比CYP 1B 1更显著。相反，其他抗癫痫药物（卡马西平、拉莫三嗪、左乙拉西坦、苯妥英）不影响3-MC介导的CYP 1B 1和CYP 1A 1上调。已知VPA作为组蛋白脱乙酰酶（HDAC）抑制剂发挥作用。因此，检查了代表性HDAC抑制剂阿司他汀A对3-MC诱导CYP 1的影响。曲古抑菌素A可增强3-MC对CYP 1A 1的诱导作用，但对CYP 1B 1无明显影响。
AimsThis study was performed to investigate the expression profile of cytochrome P450 (CYP) isoforms and effects of polycyclic aromatic hydrocarbons (PAHs) and antiepileptic drugs on CYP1 expression in human astrocytoma MOG-G-CCM cells.Main methodsCYP1A1 and CYP1B1 expression were determined by quantitative real-time polymerase chain reaction, Western blotting, and immunocytochemistry.Key findingsMOG-G-CCM cells expressed various CYP isoforms. Among the CYP isoforms analyzed, CYP1B1 showed the highest expression level, followed by CYP1A1. Furthermore, CYP1B1 was localized in both the endoplasmic reticulum and mitochondria. 3-Methylcholanthrene (3-MC), benz[a]anthracene (B[a]A), benzo[a]pyrene (B[a]P), and valproic acid (VPA) increased the expression of CYP1B1 and CYP1A1. The potent aryl hydrocarbon receptor antagonist GNF351 significantly suppressed the 3-MC- and VPA-mediated upregulation of CYP1B1 and CYP1A1. In addition, VPA potentiated the induction of CYP1B1 and CYP1A1 by 3-MC, B[a]A, and B[a]P, although the augmentation of CYP1A1 was more remarkable than that of CYP1B1. In contrast, other antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, phenytoin) did not affect the 3-MC-mediated upregulation of CYP1B1 and CYP1A1. VPA is known to act as a histone deacetylase (HDAC) inhibitor. Therefore, the effects of trichostatin A, a representative HDAC inhibitor, on CYP1 induction by 3-MC were examined. Trichostatin A enhanced the 3-MC-mediated upregulation of CYP1A1 but not CYP1B1.SignificanceThese results partially indicated that VPA may augment the PAH-mediated induction of CYP1B1 and CYP1A1 through the activation of transcription by HDAC inhibition.