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Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration

  • Wang, Jianle;Nisar, Majid;Huang, Chongan;Pan, Xiangxiang;Lin, Dongdong;Zheng, Gang;Jin, Haiming;Chen, Deheng;Tian, Naifeng;Huang, Qianyu;Duan, Yue;Yan, Yingzhao;Wang, Ke;Wu, Congcong;Hu, Jianing;Zhang, Xiaolei;Wang, Xiangyang
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.5.1-5.14
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    • 2018

  • Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol ($10{\mu}M$) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-$1{\alpha}$ signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.

  • https://doi.org/10.1038/s12276-018-0173-3 인용 KSCI

Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach

  • Tae-Han Kim ;In-Ho Kim ;Seung Joo Kang;Miyoung Choi;Baek-Hui Kim ;Bang Wool Eom;Bum Jun Kim;Byung-Hoon Min;Chang In Choi ;Cheol Min Shin;Chung Hyun Tae;Chung sik Gong;Dong Jin Kim;Arthur Eung-Hyuck Cho;Eun Jeong Gong;Geum Jong Song;Hyeon-Su Im;Hye Seong Ahn;Hyun Lim;Hyung-Don Kim;Jae-Joon Kim;Jeong Il Yu;Jeong Won Lee;Ji Yeon Park;Jwa Hoon Kim;Kyoung Doo Song;Minkyu Jung;Mi Ran Jung;Sang-Yong Son;Shin-Hoo Park;Soo Jin Kim;Sung Hak Lee;Tae-Yong Kim;Woo Kyun Bae;Woong Sub Koom;Yeseob Jee;Yoo Min Kim;Yoonjin Kwak;Young Suk Park;Hye Sook Han;Su Youn Nam;Seong-Ho Kong
    • Journal of Gastric Cancer
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    • v.23 no.2
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    • pp.365-373
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    • 2023

  • https://doi.org/10.5230/jgc.2023.23.e20 인용 PDF