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

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 rema...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232087/
https://www.ncbi.nlm.nih.gov/pubmed/30420619
http://dx.doi.org/10.1038/s12276-018-0173-3
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author 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
author_facet 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
author_sort Wang, Jianle
collection PubMed
description 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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spelling pubmed-62320872018-11-16 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 Exp Mol Med Article 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. Nature Publishing Group UK 2018-11-12 /pmc/articles/PMC6232087/ /pubmed/30420619 http://dx.doi.org/10.1038/s12276-018-0173-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title_full Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title_fullStr Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title_full_unstemmed Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title_short Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration
title_sort small molecule natural compound agonist of sirt3 as a therapeutic target for the treatment of intervertebral disc degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232087/
https://www.ncbi.nlm.nih.gov/pubmed/30420619
http://dx.doi.org/10.1038/s12276-018-0173-3
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