HSP70 attenuates compression-induced apoptosis of nucleus pulposus cells by suppressing mitochondrial fission via upregulating the expression of SIRT3.
HSP70 attenuates compression-induced apoptosis of nucleus pulposus cells by suppressing mitochondrial fission via upregulating the expression of SIRT3.
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HSP70 通过上调 SIRT3 的表达抑制线粒体裂变，从而减轻压迫诱导的髓核细胞凋亡
DOI：
10.1038/s12276-022-00745-9
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发表时间：
2022-03
影响因子：
12.8
通讯作者：
Shao Z
中科院分区：
文献类型：
--
作者：
Hu B;Wang P;Zhang S;Liu W;Lv X;Shi D;Zhao L;Liu H;Wang B;Chen S;Shao Z
压迫诱导的髓核细胞凋亡在椎间盘退变(IVDD)的发病机制中起着关键作用。最近的研究表明，线粒体分裂和融合的失调与多种疾病的发病有关。然而，它在压迫诱导的NP细胞凋亡中的作用和调节作用尚未完全阐明。热休克蛋白70(HSP70)是一种主要的细胞保护性热休克蛋白，但其在IVDD中的生理作用，特别是对线粒体分裂和融合的影响尚不清楚。在这里，我们发现压迫可以诱导线粒体分裂，最终通过线粒体凋亡途径触发NP细胞的凋亡。此外，我们还鉴定了HSP70对NP细胞的细胞保护作用，我们发现在体内外促进HSP70的表达可以保护NP细胞免受异常机械负荷的影响。最后，我们发现HSP70通过促进SIRT3的表达来抑制压迫诱导的线粒体分裂，从而减轻线粒体功能障碍和活性氧的产生，最终抑制NP细胞中线粒体的凋亡途径。综上所述，我们的结果表明，HSP70可以通过上调SIRT3的表达来抑制线粒体的分裂，从而减轻压迫诱导的NP细胞的凋亡。促进HSP70的表达可能成为IVDD治疗的新策略。
Compression-induced apoptosis of nucleus pulposus (NP) cells plays a pivotal role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have shown that the dysregulation of mitochondrial fission and fusion is implicated in the pathogenesis of a variety of diseases. However, its role in and regulatory effects on compression-induced apoptosis of NP cells have not yet been fully elucidated. Heat shock protein 70 (HSP70) is a major cytoprotective heat shock protein, but its physiological role in IVDD, especially its effect on mitochondrial fission and fusion, is still unknown. Herein, we found that compression could induce mitochondrial fission, which ultimately trigger apoptosis of NP cells via the mitochondrial apoptotic pathway. In addition, we identified the cytoprotective effects of HSP70 on NP cells, and we found that promoting the expression of HSP70 could protect NP cells from abnormal mechanical loading in vitro and in vivo. Finally, we showed that HSP70 inhibited compression-induced mitochondrial fission by promoting SIRT3 expression, thereby attenuating mitochondrial dysfunction and the production of reactive oxygen species and ultimately inhibiting the mitochondrial apoptotic pathway in NP cells. In conclusion, our results demonstrated that HSP70 could attenuate compression-induced apoptosis of NP cells by suppressing mitochondrial fission via upregulating SIRT3 expression. Promoting the expression of HSP70 might be a novel strategy for the treatment of IVDD.
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DOI：
10.1124/jpet.104.067926
发表时间：
2004-08-01
影响因子：
3.5
作者：
Liu, J;Kam, KWL;Wong, TM
通讯作者：
Wong, TM
影响因子：
7.2
作者：
Ding, Fan;Shao, Zeng-Wu;Xiong, Li-Ming
通讯作者：
Xiong, Li-Ming
影响因子：
11.4
作者：
Jin Q;Li R;Hu N;Xin T;Zhu P;Hu S;Ma S;Zhu H;Ren J;Zhou H
通讯作者：
Zhou H
影响因子：
8
作者：
Mayer, MP;Bukau, B
通讯作者：
Bukau, B
DOI：
10.1002/jbmr.4019
发表时间：
2020-08
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Madhu V;Boneski PK;Silagi E;Qiu Y;Kurland I;Guntur AR;Shapiro IM;Risbud MV
通讯作者：
Risbud MV