Life sciences · 2019
Renalase attenuates mitochondrial fission in cisplatin-induced acute kidney injury via modulating sirtuin-3.
СтатьяНазвание и аннотация: Перевод в очереди
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Huang Zhimin, Li Qing, Yuan Yanggang, Zhang Chengning, Wu Lin, Liu Xi, Cao Wei, Guo Honglei, Duan Suyan, Xu Xueqiang, Zhang Bo, Xing Changying
Аннотация
AIMS: Acute kidney injury (AKI) can limit the clinical use of cisplatin in cancer treatment. The drivers of cisplatin-induced AKI include oxidative stress, mitochondrial dysfunction and apoptosis. Previous studies showed renalase protected cultured human renal proximal tubular cell (HK-2) against cisplatin induced necrosis, and renalase-knockout mice subjected to cisplatin showed exacerbated kidney injury. Therefore, it is necessary to determine the exact mechanisms of renalase in cisplatin-induced nephrotoxicity.
MAIN METHODS: To study the protective effect of renalase on cell viability, renal function, apoptosis, reactive oxygen species (ROS) production and mitochondrial dynamics, cultured HK-2 cells and male mice were subjected to cisplatin. Signaling proteins related to apoptosis, survival, and mitochondrial fission were analyzed by Western blot.
KEY FINDINGS: In this study, we showed that the protective effect of recombinant renalase in cisplatin-induced AKI was associated with the regulation of ROS production, mitochondrial dynamics and sirtuin-3 (Sirt3) levels in vivo and in vitro. After cisplatin treatment, recombinant renalase restored Sirt3 expression, reduced mitochondrial fission and ROS generation. In HK-2 cells, downregulation of endogenous Sirt3 expression by siRNA transfection abrogated the renalase cytoprotection.
SIGNIFICANCE: Our study suggests that renalase protects against cisplatin-induced AKI by improving mitochondrial function and inhibiting oxidative stress, and in vitro, it functions in a Sirt3-dependent manner.
MAIN METHODS: To study the protective effect of renalase on cell viability, renal function, apoptosis, reactive oxygen species (ROS) production and mitochondrial dynamics, cultured HK-2 cells and male mice were subjected to cisplatin. Signaling proteins related to apoptosis, survival, and mitochondrial fission were analyzed by Western blot.
KEY FINDINGS: In this study, we showed that the protective effect of recombinant renalase in cisplatin-induced AKI was associated with the regulation of ROS production, mitochondrial dynamics and sirtuin-3 (Sirt3) levels in vivo and in vitro. After cisplatin treatment, recombinant renalase restored Sirt3 expression, reduced mitochondrial fission and ROS generation. In HK-2 cells, downregulation of endogenous Sirt3 expression by siRNA transfection abrogated the renalase cytoprotection.
SIGNIFICANCE: Our study suggests that renalase protects against cisplatin-induced AKI by improving mitochondrial function and inhibiting oxidative stress, and in vitro, it functions in a Sirt3-dependent manner.