Autophagy inhibits C2-ceramide-mediated cell death by decreasing the reactive oxygen species levels in SH-SY5Y cells. (9th June 2017)

• Record Type: Journal Article
• Authors: Fan, Chenghe; Liu, Yuanyuan; Zhao, Mingming; Zhan, Rui; Cui, Wei; Jin, Haiqiang; Teng, Yuming; Lv, Pu; Zheng, Lemin; Huang, Yining
• Is Part Of: Neuroscience letters. Volume 651(2017)
• Page Start: 198
• Page End: 206
• Publication Date: 2017-06-09
• Subjects: Atg autophagy-related proteins -- mTOR mammalian target of rapamycin -- Akt/PKB protein kinase B -- JNK c-Jun N-terminal kinase -- ROS reactive oxygen species -- ERK extracellular signal-regulated kinase -- 3-MA 3-methyadenine -- H2DCFDA 2′, 7′-dichlorofluorescin diacetate -- DMSO dimethyl sulphoxide -- PBS phosphate buffer saline -- BSA bovine serum albumin -- DAPI 4′, 6-diamidino-2-phenylindole -- TEM transmission electron microscopy -- ER endoplasmic reticulum -- LC3 microtubulesas sociated protein light -- MEK MAPK/ERK kinase -- NAC N-acetyl-l-cysteine; C2-ceramide -- Autophagy -- Apoptosis -- Reactive oxygen species (ROS); Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.03.006
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: C2-ceramide induces caspase-3-independent SH-SY5Y cell death. C2-ceramide induces autophagy through ERK1/2 pathway in SH-SY5Y cells. Autophagy inhibits C2-ceramide-induced SH-SY5Y cell death by decreasing ROS production. 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.