1. Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury.
- Author
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Qian, Yingying, Guo, Xiangjiang, Che, Lin, Guan, Xuejing, Wu, Bei, Lu, Renhua, Zhu, Mingli, Pang, Huihua, Yan, Yucheng, Ni, Zhaohui, and Gu, Leyi
- Subjects
OXIDATIVE stress ,KIDNEY disease treatments ,TREATMENT of reperfusion injuries ,IMMUNOBLOTTING ,IMMUNOFLUORESCENCE - Abstract
Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process.Background/Aims: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or HMethods: 2 O2 . Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein andN -acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1β, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or HResults: 2 O2 . Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in bothin vivo andin vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition. [ABSTRACT FROM AUTHOR]Conclusion: - Published
- 2018
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