title: Autophagy inhibits C2-ceramide-mediated cell death by decreasing the reactive oxygen species levels in SH-SY5Y cells.
abstract: Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2. However, only inhibition of ERK1/2 with PD98059 prevented C2-ceramide-induced autophagy, indicating that the ERK1/2 pathway contributes to ceramide-induced autophagy. According to the results of the flow cytometric assays, C2-ceramide-induced cell death was increased by 3-methyadenine (3-MA) and decreased by rapamycin. Furthermore, the generation of reactive oxygen species (ROS) in the cells was increased by 3-MA and decreased by rapamycin. Based on these datas, autophagy protected SH-SY5Y cells from C2-ceramide-induced cell death by decreasing ROS production. Therapeutic strategies that regulate autophagy may be used in the treatment of neurological disorders associated with ceramide-induced cell death.
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China; The Institute of Small Vessel Disease of the Nervous System, Peking University, Beijing Key Laboratory, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Chenghe
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Lv
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: zhengl@bjmu.edu.cn.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China; The Institute of Small Vessel Disease of the Nervous System, Peking University, Beijing Key Laboratory, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. Electronic address: ynhuang@bjmu.edu.cn.
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
mesh_terms: D001343:Autophagy; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D020935:MAP Kinase Signaling System; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C064769:N-acetylsphingosine; D017382:Reactive Oxygen Species; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine
keywords: Apoptosis; Autophagy; C2-ceramide; Reactive oxygen species (ROS)