INTRACELLULAR CALCIUM ION-RELATED GENE EXPRESSION OF CYTOCHROMES P450

细胞色素 P450 的细胞内钙离子相关基因表达

• 批准号: 10672104
• 负责人: DEGAWA Masakuni
• 金额: $ 2.37万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672104/
• 关键词: CYTOCHROME P450; CYP; GENE REGULATION; CALCIUM; CALCIUM CHANNEL BLOCKER; RAT; CULTURED HEPATOCYTE; LIVER; チトクロームP450; CYPIA; CYP3A; CYP2E; 肝細胞

We have previously reported that calcium channel bockers such as nicardipine, verapamil and cinnarizine induce cytochromes P450 (CYP1A2, 3A1/3A2, 2B1/2B2 and 2E1) in the rat liver. In the present study, to determine whether all calcium channel blockers show the inductive activity for cytochromes P450 (CYP1A2, 3A1/3A2, 2B1/2B2 and 2E1), we first examined the induction of the CYPs in the rat liver by the metal ions, CoィイD12+ィエD1 and NiィイD12+ィエD1, which were characterized as calcium channel blockers, and found that these metal ions induced CYP1A2, while suppressed the gene expression of other CYPs. These suggest that the gene expression of CYPs with exception of CYP1A2 is not necessarily associated with intracellular calcium ion concentration. On the other hand, a cultured hepatic cell line is thought to be a useful tool for investigating the mechanism of gene expression of CYPs because there is a heterogeneity in liver cells. Therefore, we examined the gene expression of CYPs by RT-PCR using the cell line, which was previously established from male SD rat liver, and the results suggest that the gene expression of CYPs, especially CYP2B2 and 3A1/2, is mainly regulated by cytoplasmic suppressive factor(s) rather than by intracellular calcium ion.

我们先前已经报道说，大鼠肝脏中的钙通道岩（如尼卡迪平，维拉帕米和肉毒药）诱导细胞色素P450（CYP1A2、3A1/3A2、2B1/2B2和2E1）。 In the present study, to determine whether all calcium channel blockers show the inductive activity for cytochromes P450 (CYP1A2, 3A1/3A2, 2B1/2B2 and 2E1), we first examined the induction of the CYPs in the rat liver by the metal ions, Coi D12+iye D1 and Niye D12+iye D1, which were characterized as calcium channel blockers,并发现这些金属离子诱导CYP1A2，同时抑制了其他CYP的基因表达。这些表明，除了CYP1A2以外，CYP的基因表达不一定与细胞内钙离子浓度有关。另一方面，培养的肝细胞系被认为是研究CYP基因表达机制的有用工具，因为肝细胞中存在异质性。因此，我们使用RT-PCR使用细胞系检查了CYP的基因表达，该细胞系先前是从雄性SD大鼠肝脏中确定的，结果表明，CYP的基因表达，尤其是CYP2B2和3A1/2，主要是由细胞质抑制因子（S）调节，而不是由细胞内细胞校立钙化。