SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells.
SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells.
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SIRT1 通过促进退变的人椎间盘髓核细胞的自噬来防止细胞凋亡。
DOI：
10.1038/srep07456
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发表时间：
2014-12-12
影响因子：
4.6
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Jiang W;Zhang X;Hao J;Shen J;Fang J;Dong W;Wang D;Zhang X;Shui W;Luo Y;Lin L;Qiu Q;Liu B;Hu Z
SIRT 1可以保护退化的人NP细胞免于凋亡，凋亡与自噬之间存在广泛而密切的联系。到目前为止，自噬在人类IVD退化过程中的作用尚不清楚。我们试图探索自噬和人类IVD变性之间的关系，并了解自噬是否参与SIRT 1对NP细胞凋亡的保护作用。结果表明，DDD组自噬体数量减少，LC 3和Beclin-1的mRNA水平降低，LC 3-II/I和Beclin-1的蛋白表达降低。白藜芦醇可增加LC 3-II/I和Beclin-1蛋白表达，减少NP细胞凋亡。与此相反，在烟酰胺或SIRT 1-siRNA转染处理中，LC 3-II/I和Beclin-1的蛋白水平下调，凋亡水平显著上调。进一步分析发现，无论是否加入白藜芦醇，巴弗洛霉素A预处理均显著增加了切割的Caspase 3的表达和凋亡发生率。提示自噬可能在IVD退变中起重要作用，SIRT 1通过促进自噬保护退变的人NP细胞免于凋亡。这些发现将有助于发展新的治疗方法退行性椎间盘疾病的治疗。
SIRT1 could protect degenerative human NP cells against apoptosis, and there were extensive and intimate connection between apoptosis and autophagy. Up to now, the role of autophagy in the process of human IVD degeneration is unclear. We sought to explore the relationship between autophagy and human IVD degeneration and to understand whether autophagy is involved in the protective effect of SIRT1 against apoptosis in NP cells. Our results showed that the autophagosomes number, the mRNA level of LC3 and Beclin-1, the protein expression of LC3-II/I and Beclin-1, decreased in NP from DDD. Resveratrol could increase the protein expression of LC3-II/I and Beclin-1, and reduce apoptosis in degenerative NP cells. In contrast, the protein levels of LC3-II/I and Beclin-1 were down-regulated and apoptosis level was significantly up-regulated in treatment with nicotinamide or SIRT1-siRNA transfection. Further analysis identified that the expression of cleaved Caspase3 and apoptosis incidence significantly increased with the pretreatment of bafilomycin A, whether resveratrol was added or not. These suggested that autophagy may play an important role in IVD degeneration, and SIRT1 protected degenerative human NP cells against apoptosis via promoting autophagy. These findings would aid in the development of novel therapeutic approaches for degenerative disc disease treatment.
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影响因子：
3
作者：
Gruber, HE;Hanley, EN
通讯作者：
Hanley, EN
影响因子：
2.4
作者：
Hunter, CJ;Matyas, JR;Duncan, NA
通讯作者：
Duncan, NA
DOI：
10.1073/pnas.0712145105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Lee, In Hye;Cao, Liu;Finkel, Toren
通讯作者：
Finkel, Toren
白藜芦醇通过 AMPK/SIRT1 途径上调自噬，保护 HUVEC 免受氧化 LDL 诱导的氧化损伤
影响因子：
3.4
作者：
Guo, Hualei;Chen, Yanling;Wu, Weikang
通讯作者：
Wu, Weikang
影响因子：
--
作者：
Gagarina, Viktoria;Gabay, Odile;Dvir-Ginzberg, Mona;Lee, Eun Jin;Brady, Jillian K.;Quon, Michael J.;Hall, David J.
通讯作者：
Hall, David J.