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Annexin A5 as a New Potential Biomarker for Cisplatin-lnduced Toxicity in Human Kidney Epithelial Cells

机译:Annexin A5作为顺铂诱导的人肾脏上皮细胞毒性的新的潜在生物标志物。

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摘要

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNAand ultimately cancer cell apop-tosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.
机译:顺铂是含铂抗癌药物的一种,该药物引起DNA交联并最终导致癌细胞凋亡。顺铂对各种类型癌症的治疗作用已被广泛报道,但已一起发现了副作用,并且肾毒性被认为是顺铂的主要副作用。为了选择新的敏感的肾毒性生物标志物的候选者,我们使用2-DE / MALDI-TOF-MS进行了蛋白质组学分析,然后在人肾细胞株HK-2细胞中进行了顺铂处理,并将结果与​​由基因从以前报道的顺铂表达改变。膜联蛋白A5已被选为最有潜力的候选物,并且已通过Western印迹,RT-PCR和细胞生存力测定法鉴定了膜联蛋白A5是否可作为敏感的肾毒性生物标志物。顺铂对HK-2细胞的处理导致膜联蛋白A5蛋白和mRNA水平的表达增加。膜联蛋白A5的过表达阻止HK-2细胞增殖,表明膜联蛋白A5与肾细胞毒性之间的相关性。两者合计,这些结果表明膜联蛋白A5作为顺铂介导的肾毒性的新生物标志物的可能性。

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