title: SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Rehabilitation Medicine, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd., Chongqing, 400016, China.
authors.forename: Dawu
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shui
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Liangbo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Quanhe
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001343:Autophagy; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000201:enzymology* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D056564:Sirtuin 1 / Q000502:physiology*; D055815:Young Adult
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1