ZLN005 protects against ischemia-reperfusion-induced kidney injury by mitigating oxidative stress through the restoration of mitochondrial fatty acid oxidation.

Autor:	Wang Z; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Fu Z; Department of Nephrology, Zhongshan Hospital, Fudan University Shanghai 200032, China., Wang C; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Xu J; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Ma H; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Jiang M; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Xu T; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Feng X; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China., Zhang W; Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
Jazyk:	angličtina
Zdroj:	American journal of translational research [Am J Transl Res] 2021 Sep 15; Vol. 13 (9), pp. 10014-10037. Date of Electronic Publication: 2021 Sep 15 (Print Publication: 2021).
Abstrakt:	To date, the treatment of acute kidney injury (AKI) remains a difficult problem for clinicians. In the present study, we assessed whether ZLN005, a novel peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) agonist, can protect against ischemic AKI in vivo and in vitro. Notably, ZLN005 treatment significantly alleviated Ischemia-reperfusion (I/R)-induced tubular injury and reversed the decrease in hypoxia-reoxygenation-induced cell viability by restoring PGC-1α expression in a dose-dependent manner. This beneficial effect of ZLN005 was associated with the preservation of mitochondrial fatty acid oxidation (MitoFAO) and the alleviation of oxidative stress. Cotreatment with etomoxir, a specific inhibitor of carnitine palmitoyltransferase-1α (CPT-1α) activity, or CPT-1α siRNA abrogated ZLN005-induced antistress responses by mitigating reactive oxygen species production and decreasing apoptosis under ischemia-hypoxia conditions by suppressing MitoFAO. Further studies revealed that activation of endoplasmic reticulum (ER) stress may be involved in the effect of CPT-1α inhibition observed in vivo and in vitro. Collectively, our results suggest that ZLN005 confers a protective effect on I/R-induced kidney injury by mitigating ER stress through the restoration of MitoFAO by targeting PGC-1α. Competing Interests: None. (AJTR Copyright © 2021.)
Databáze:	MEDLINE
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