title: Hypoxia facilitates the survival of nucleus pulposus cells in serum deprivation by down-regulating excessive autophagy through restricting ROS generation.
abstract: Nucleus pulposus (NP) cells reside in a hypoxic environment in vivo, while the mechanisms of how NP cells maintain survival under hypoxia are not clear. Autophagy is an important physiological response to hypoxia and implicated in the survival regulation in most types of cells. This study was designed to investigate the role of autophagy in the survival of NP cells under hypoxia. We found that appropriate autophagy activity was beneficial to the survival of NP cells in serum deprivation, while excessive autophagy led to death of the NP cells. Hypoxia facilitated the survival of NP cells in serum deprivation by down-regulating excessive autophagy. Hypoxia down-regulated the autophagy activity of NP cells through restricting the production of reactive oxygen species (ROS) and inactivating the AMPK/mTOR signaling pathway, and possibly through a pathway involving HIF-1α. We believed that understanding the autophagy response of NP cells to hypoxia and its role in cell survival had important clinical significance in the prevention and treatment of degenerative discogenic diseases.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Jiang-Wei
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Ni
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Sheng-Dan
authors.initials: SD
authors.lastname: Jiang
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Electronic address: jiangleisheng@126.com.
authors.forename: Lei-Sheng
authors.initials: LS
authors.lastname: Jiang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015687:Cell Hypoxia; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007403:Intervertebral Disc / Q000166:cytology*; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase
keywords: Apoptosis; Autophagy; Hypoxia; Nucleus pulpopus cells; ROS