title: 1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy.
abstract: OBJECTIVE
  Dysregulation of the autophagy pathway has been suggested as an important mechanism in the pathogenesis of Parkinson's disease (PD). Therefore, modulation of autophagy may be a novel strategy for the treatment of PD. Recently, an active form of vitamin D₃ has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D₃ (calcitriol) in an in vitro model of Parkinson's disease.
  
  
  METHODS
  An in vitro model of Parkinson's disease, the rotenone-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels and analyzed autophagy-associated intracellular signaling proteins by Western blotting.
  
  
  RESULTS
  Rotenone treatment of SH-SY5Y cells reduced their viability. This treatment also increased reactive oxygen species levels and decreased levels of intracellular signaling proteins associated with cell survival; simultaneous exposure to calcitriol significantly reversed these effects. Additionally, calcitriol increased levels of autophagy markers, including LC3, beclin-1, and AMPK. Rotenone inhibited autophagy, as indicated by decreased beclin-1 levels and increased mTOR levels, and this effect was reversed by calcitriol treatment.
  
  
  CONCLUSIONS
  Calcitriol protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy signaling pathways such as those involving LC3 and beclin-1. These neuroprotective effects of calcitriol against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for its clinical use in the treatment of PD.
authors: Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea. Electronic address: neveu@gnah.co.kr.
authors: Wooyoung
authors: W
authors: Jang
authors: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors: Hee Ju
authors: HJ
authors: Kim
authors: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors: Huan
authors: H
authors: Li
authors: Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.
authors: Kwang Deog
authors: KD
authors: Jo
authors: Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.
authors: Moon Kyu
authors: MK
authors: Lee
authors: Department of Rehabilitation Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.
authors: Sun Hong
authors: SH
authors: Song
authors: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea. Electronic address: hoyang@kist.re.kr.
authors: Hyun Ok
authors: HO
authors: Yang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002117:Calcitriol / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C494826:BAX protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D020011:Protective Agents; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; D002117:Calcitriol
keywords: Autophagy; Calcitriol; Neuroprotection; Parkinson’s disease