Autophagy protects the rotenone-induced cell death in alpha-synuclein overexpressing SH-SY5Y cells.
Loss of dopaminergic cells induced by alpha-synuclein accumulation in substantia nigra causes the development of Parkinson's disease (PD). To date, although autophagy has been implicated in the pathology of PD, the molecular mechanism is still unclear. To study the role of autophagy in PD pathogenesis, we established stable SH-SY5Y cell lines overexpressing wild-type or mutant alpha-synuclein proteins (A30P or A53T). Overexpression of mutant alpha-synuclein induced some protein aggregates and cell death in the absence of drug. LC3-II protein, a critical marker for autophagy, was produced in an autophagy-dependent manner. The rotenone-induced cell death was interrupted by autophagy stimulation. Autophagy activation also restored the mitochondrial membrane potential (MMP) impaired by rotenone in mutant alpha-synuclein expressing cells. Additionally, autophagy activation significantly relieved rotenone-induced ROS accumulation and HIF-1alpha expression in neuronal cells expressing mutant alpha-synuclein proteins. These findings indicate that autophagy plays an important scavenger role against harmful influence of toxic protein aggregates produced in rotenone-treated cells.
Dadakhujaev
Shorafidinkhuja
S
Department of Biochemistry and Neurobiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, 92 Chilam-Dong, Jinju, GyeongNam 660-751, Republic of Korea.
Noh
Hae Sook
HS
Jung
Eun Joo
EJ
Cha
Joon Yung
JY
Baek
Seon Mi
SM
Ha
Ji Hye
JH
Kim
Deok Ryong
DR
D001343:Autophagy; D016923:Cell Death; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D012402:Rotenone / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D051844:alpha-Synuclein; D012402:Rotenone; D004298:Dopamine