title: Insulin on activation of autophagy with integrins and syndecans against MPP+-induced α-synuclein neurotoxicity.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly caused by dopaminergic neuronal cell death. Human neuroblastoma SH-SY5Y cells differentiated by retinoic acid have been used to study the in vitro PD model induced by 1-methyl-4-phenyl pyridinium (MPP+). In this study, pretreatment of insulin inhibited MPP+-induced cell membrane damages, which also inhibited the Cox-2 and α-synuclein levels. In addition, MPP+and/or insulin enhanced the autophagy LC3. Furthermore, MPP+-induced neurotoxicity diminished the integrins β3, αV and induced the syndecan-1 and -3. Insulin pretreatment enhanced the phosphorylation of integrin-linked kinase and further induced the integrin and syndecan molecules. These findings suggest that insulin prevents MPP+-induced α-synuclein apoptosis through the activation of integrin and syndecan pathways in SH-SY5Y+RA cells.
authors.affiliation: Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Ramalingam
authors.affiliation: Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: kimsj@khu.ac.kr.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D017209:Apoptosis; D001343:Autophagy; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D053667:Syndecans / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D007328:Insulin; D016023:Integrins; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D053667:Syndecans; D051844:alpha-Synuclein; D014212:Tretinoin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015655:1-Methyl-4-phenylpyridinium
keywords: Cox-2; ILK; Neurodegenerative; Parkinson’s disease; SH-SY5Y