Cisplatin-mediated通过诱导细胞毒性CYP4A 11人类肾小管上皮细胞表达。
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李,李D,领带C,吴J,吴问,李问
Cisplatin-mediated通过诱导细胞毒性CYP4A 11人类肾小管上皮细胞表达。
J Toxicol Sci。2015年12月,40 (6):895 - 900。doi: 10.2131 / jts.40.895。
- PubMed ID
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26558470 (在PubMed]
- 文摘
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顺铂(CP)是一种主要的抗肿瘤药治疗实体肿瘤,但它有剂量依赖性肾小管毒性。之前的研究表明,诱导细胞色素P450 (CYP) CP可能发挥作用在CP的肾损伤。本研究的目的是调查CP-induced毒性之间的关系和CYP4A11表达在人类肾小管上皮细胞(HK-2)。20-Hydroxyeicosatetraenoic酸(20-HETE)是一个CYP4A11的花生四烯酸代谢物在肾损伤中起着重要的作用。乳酸脱氢酶(LDH)的活性是由分光光度计。CYP4A11表达式被免疫细胞化学分析。CYP4A11 mRNA和蛋白表达进行评估通过rt - pcr和免疫印迹分析。结果表明,20-HETE(1、10、50妈妈),一个CYP4A11花生四烯酸的代谢产物明显增加乳酸脱氢酶(LDH)释放在这些细胞。当CP (10 (4) M)和20-HETE(1、10、50妈妈)co-applied这些细胞,CP-induced LDH释放被20-HETE大大夸大了。此外,安妥明CYP4A诱导物,也增加了在CP-treated细胞LDH释放。相比之下,CYP4A抑制剂N-Hydrocy-N”——(4-butyl-2-methylphenyl) formamidine (het - 0016)减少在CP-treated细胞LDH释放。 Immunocytochemical analysis showed that CYP4A11expression was much stronger in CP-(10(-4) M) treated cells than that in clofibrate-treated cells. Further RT-PCR and Western blot analyses demonstrated that CYP4A11 mRNA and protein expression were significantly up-regulated in CP- (10(-4) M) treated cells compared to the clofibrate group. The findings of this study indicate that CP is a potent inducer of CYP4A11, and it exerts its toxic functions via the induction of CYP4A11 and 20-HETE generation.