title: Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y.
abstract: Recent studies have shown that autophagy upregulation may be a tractable therapeutic intervention for clearing the disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in Parkinson's disease (PD). In this study, we explored a novel pharmacotherapeutic approach to treating PD by utilizing potential autophagy enhancers valproic acid (VPA) and carbamazepine (CBZ). Pretreatment with VPA (3 mM) and CBZ (50 μM) along with positive control rapamycin (Rap, 0.2 μM) or lithium (LiCl, 10 mM) significantly enhanced cell viability, decreased rotenone-induced nuclear fragmentation and apoptosis, ameliorated the decrease in mitochondrial membrane potential, reduced reactive oxygen species generation in the human neuroblastoma SH-SY5Y cells. Specifically, the numbers of lysosomes and autophagic vacuolar organelles were increased and the microtubule-associated protein 1 light chain 3-II (LC3-II) expression was up-regulated by VPA, CBZ, Rap, and LiCl (53%, 31%, 72%, and 63%), suggesting that these agents activated autophagic pathways. Moreover, pretreatment with the autophagy inhibitor chloroquine (Chl, 10 μM) remarkably strengthened rotenone toxicity in these cells. Our results suggest that VPA and CBZ, the most commonly used anti-epilepsy and mood-stabilizing medications with low-risk and easy administration might be potential therapeutics for PD.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China.
authors: N
authors: N
authors: Xiong
authors: M
authors: M
authors: Jia
authors: C
authors: C
authors: Chen
authors: J
authors: J
authors: Xiong
authors: Z
authors: Z
authors: Zhang
authors: J
authors: J
authors: Huang
authors: L
authors: L
authors: Hou
authors: H
authors: H
authors: Yang
authors: X
authors: X
authors: Cao
authors: Z
authors: Z
authors: Liang
authors: S
authors: S
authors: Sun
authors: Z
authors: Z
authors: Lin
authors: T
authors: T
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002220:Carbamazepine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease; D017382:Reactive Oxygen Species; D012402:Rotenone / Q000633:toxicity; D014475:Uncoupling Agents / Q000633:toxicity; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; D002220:Carbamazepine; D014635:Valproic Acid