Wang Ying, Liu Zhiwen, Shu Shaoqun, Cai Juan, Tang Chengyuan, Dong Zheng
Department of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China.
Department of Cellular Biology and Anatomy, Charlie Norwood Veterans Affair Medical Center, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Front Physiol. 2020 Dec 17;11:619730. doi: 10.3389/fphys.2020.619730. eCollection 2020.
Autophagy is a conserved, multistep pathway that degrades and recycles dysfunctional organelles and macromolecules to maintain cellular homeostasis. Mammalian target of rapamycin (mTOR) and adenosine-monophosphate activated-protein kinase (AMPK) are major negative and positive regulators of autophagy, respectively. In cisplatin-induced acute kidney injury (AKI) or nephrotoxicity, autophagy is rapidly induced in renal tubular epithelial cells and acts as a cytoprotective mechanism for cell survival. Both mTOR and AMPK have been implicated in the regulation of autophagy in cisplatin-induced AKI. Targeting mTOR and/or AMPK may offer effective strategies for kidney protection during cisplatin-mediated chemotherapy.
自噬是一种保守的多步骤途径,可降解和回收功能失调的细胞器和大分子,以维持细胞内稳态。雷帕霉素哺乳动物靶点(mTOR)和单磷酸腺苷激活蛋白激酶(AMPK)分别是自噬的主要负性和正性调节因子。在顺铂诱导的急性肾损伤(AKI)或肾毒性中,肾小管上皮细胞中自噬迅速被诱导,并作为细胞存活的一种细胞保护机制。mTOR和AMPK都参与了顺铂诱导的AKI中自噬的调节。靶向mTOR和/或AMPK可能为顺铂介导的化疗期间的肾脏保护提供有效的策略。