SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells.
Wei Jiang, Xuemei Zhang, Jie Hao, Jieliang Shen, Ji Fang, Wen Dong, Dawu Wang, Xiaojun Zhang, Wei Shui, Yi Luo, Liangbo Lin, Quanhe Qiu, Bin Liu, Zhenming Hu
Author Information
Wei Jiang: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xuemei Zhang: Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jie Hao: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jieliang Shen: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ji Fang: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wen Dong: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Dawu Wang: Department of Rehabilitation Medicine, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd., Chongqing, 400016, China.
Xiaojun Zhang: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wei Shui: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yi Luo: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Liangbo Lin: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Quanhe Qiu: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Bin Liu: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Zhenming Hu: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
