title: Upregulation of cell surface estrogen receptor alpha is associated with the mitogen-activated protein kinase/extracellular signal-regulated kinase activity and promotes autophagy maturation.
abstract: Recently, accumulating evidence has implicated the dysregulation of autophagy as underlying the pathophysiology of several neurodegenerative diseases. The human neuronal cell line SH-SY5Y was exposed to 1-Methyl-4-phenylpyridinium (MPP(+)). The mechanism is that the sustained activation of the MAPK/ERK pathway by MPP(+) alters autophagy selectively at the maturation step, significant increasing in autophagy formation and delaying in autophagy degradation in SHSY5Y cells. In this study, we provided evidences that estrogen was capable of promoting SHSY5Y cells survival in MPP(+)-treated group. In particular, the up-regulation of mERα, but not mERβ, was associated with a rapid and transient activation of ERK phosphorylation compatible with promoting autophagy maturation. The up-regulation of mERα changed the sustained activation of ERK phosphorylation in MPP(+)-treated group into a temporary activation. Taken together, these findings strongly support that the expression of mERα promotes the maturation of autophagosomes into functional autolysosomes by regulating ERK, determining SHSY5Y cells survival.
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Li
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Chen-Yan
authors.initials: CY
authors.lastname: Sui
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jiangsu University Affiliated People's Hospital Jiangsu, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhou
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D015655:1-Methyl-4-phenylpyridinium
keywords: ERK; Surface estrogen receptor alpha; autophagy maturation