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KMID : 0620920180500110146
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Experimental & Molecular Medicine
2018 Volume.50 No. 11 p.146 ~ p.146
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Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
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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
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Abstract
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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?μM) 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-1α 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.
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KEYWORD
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Cell biology, Molecularly targeted therapy
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