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  2. Curcumin ameliorates CKD-induced mitochondrial dysfunction and oxidative stress through inhibiting GSK-3β activity

Curcumin ameliorates CKD-induced mitochondrial dysfunction and oxidative stress through inhibiting GSK-3β activity

  • J Nutr Biochem. 2020 Sep;83:108404. doi: 10.1016/j.jnutbio.2020.108404.
Dongtao Wang 1 Yajun Yang 2 Xiaohu Zou 3 Zena Zheng 3 Jing Zhang 3
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen 5181000, Guangdong, China; School of Chinese Medicine, Southern Medical University, Shenzhen 510515, Guangdong, China; Department of the Ministry of Science and Technology, Guangxi International Zhuang Medicine Hospital, Nanning 530201, Guangxi , China; Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen 518033, Guangdong, China. Electronic address: 95401864@qq.com.
  • 2 Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical University, Zhanjiang 524023, Guangdong , China.
  • 3 Department of Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen 5181000, Guangdong, China.
Abstract

Curcumin has been reported to attenuate muscle atrophy. However, the underling mechanism remains unclear. The aim of this study was to investigate whether curcumin could improve chronic kidney disease (CKD)-induced muscle atrophy and mitochondrial dysfunction by inhibiting glycogen synthase kinase-3β (GSK-3β) activity. The sham and CKD mice were fed either a control diet or an identical diet containing 0.04% curcumin for 12 weeks. The C2C12 myotubes were treated with H2O2 in the presence or absence of curcumin. In addition, wild-type and muscle-specific GSK-3β knockout (KO) CKD model mice were made by 5/6 nephrectomy, and the sham was regarded as control. Curcumin could exert beneficial effects, including weight maintenance and improved muscle function, increased mitochondrial biogenesis, alleviated mitochondrial dysfunction by increasing adenosine triphosphate levels, activities of mitochondrial electron transport chain complexes and basal mitochondrial respiration and suppressing mitochondrial membrane potential. In addition, curcumin modulated redox homeostasis by increasing antioxidant activity and suppressed mitochondrial oxidative stress. Moreover, the protective effects of curcumin had been found to be mediated via inhibiting GSK-3β activity in vitro and in vivo. Importantly, GSK-3β KO contributed to improved mitochondrial function, attenuated mitochondrial oxidative damage and augmented mitochondrial biogenesis in muscle of CKD. Overall, this study suggested that curcumin alleviated CKD-induced mitochondrial oxidative damage and mitochondrial dysfunction via inhibiting GSK-3β activity in skeletal muscle.

Keywords

Atrophy; Chronic kidney disease; Curcumin; Mitochondria; Skeletal muscle.

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