Sci Rep:清华大学陈立功课题组报道泰诺福韦和阿德福韦引起肾毒性的全新作用机制

2017-04-18 佚名 生物帮

2017年4月11日,国际学术权威刊物自然出版集团旗下子刊《Scientific Reports》杂志在线发表了清华大学药学院陈立功课题组在自然旗下《Scientific Reports》上发表了“Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subuni

2017年4月11日,国际学术权威刊物自然出版集团旗下子刊《Scientific Reports》杂志在线发表了清华大学药学院陈立功课题组“Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity”的研究论文,该论文报道了泰诺福韦和阿德福韦引起肾毒性方面的最新作用机制。药学院博士生赵心彬为第一作者,陈立功研究员为论文通讯作者。

核苷酸逆转录酶抑制剂泰诺福韦和阿德福韦临床上广泛用于治疗HIV感染患者,抗病毒作用高效,应用广泛。越来越多的临床案例发现,此类药物的长期服用也引起了肾毒性等毒副作用,包括急性肾损伤,慢性肾脏疾病和获得性范科尼氏综合症等。但是泰诺福韦和阿德福韦导致肾毒性的分子机制一直并没有得到阐明。

陈立功课题组通过建立泰诺福韦和阿德福韦的细胞、动物毒性模型,系统性利用蛋白组学和代谢组学等技术手段,有以下两方面重要发现:第一,泰诺福韦和阿德福韦通过下调线粒体单链DNA结合蛋白 (SSBP1) 和解旋酶 (TWINKLE)来抑制线粒体DNA复制从而产生相应的细胞毒性。第二,泰诺福韦和阿德福韦降低肿瘤坏死因子受体相关蛋白 (TRAP1) 和琥珀酸脱氢酶亚基B (SDHB) 引起细胞内葡萄糖代谢重编程,进而导致糖原聚集,增加肾毒性的风险。此发现为进一步研究核苷逆转录酶抑制剂的毒副作用提供了理论依据,并为核苷酸转录酶抑制剂药物的毒副作用治疗提供新策略。

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    2017-04-25 1ddf0692m34(暂无匿称)

    学习了!不错

    0

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    2017-04-18 圣艮山

    阻断这个有效果么

    0

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