title: Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy.
abstract: Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy.
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Dong
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Sun
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Ma
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Danjing
authors.initials: D
authors.lastname: Yang
authors.affiliation: Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin, China. Electronic address: hongwen_zhu@hotmail.com.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: xunymc2000@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Aging; Autophagy; Cellular senescence; Human neural precursor cell; MPTP