title: The protein l-isoaspartyl (d-aspartyl) methyltransferase protects against dopamine-induced apoptosis in neuroblastoma SH-SY5Y cells.
abstract: Parkinson's disease (PD) is the most common neurodegenerative motor disorder in the world. The main causes of neurodegeneration in PD are mitochondrial impairment and oxidative stress promoted by dopamine (DA) metabolism in the cytosol. Protein l-isoaspartyl (d-aspartyl) methyltransferase (PIMT) is a protein repair enzyme with anti-apoptotic properties. We previously reported that PIMT was downregulated at both gene and protein levels by DA-induced oxidative stresses in SH-SY5Y neuroblastoma cells. The purpose of the current study was to investigate the anti-apoptotic function of PIMT toward DA-induced cell death to better understand its specific neuroprotective role. Overexpression of wild-type PIMT, in contrast to its inactive mutant, protected SH-SY5Y cells from cell death and caspase 3 activation upon DA treatments. The intrinsic pathway of apoptosis as measured by caspase 9 activity was triggered by reactive oxygen species produced from DA metabolism, and overexpression of wild-type PIMT completely prevented caspase 9 activity stimulated by DA. In addition, cells overexpressing wild-type PIMT produced significantly less reactive oxygen species despite DA treatment compared to cells that do not overexpress PIMT. Together, these data indicate that DA-associated PIMT downregulation is an important event contributing to neuronal cell death. More importantly, the PIMT anti-apoptotic capacity seems to be dependent on its involvement in the cellular antioxidant machinery.
authors: Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville, Montréal, Québec H3C 3P8, Canada.
authors: D
authors: D
authors: Ouazia
authors: Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Montréal, Québec H3C 3P8, Canada.
authors: L-C
authors: LC
authors: Levros
authors: Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Montréal, Québec H3C 3P8, Canada.
authors: É
authors: É
authors: Rassart
authors: Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville, Montréal, Québec H3C 3P8, Canada. Electronic address: desrosiers.r@uqam.ca.
authors: R R
authors: RR
authors: Desrosiers
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004298:Dopamine / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D017354:Point Mutation / Q000235:genetics; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
chemical_list: D017382:Reactive Oxygen Species; C435725:PCMT1 protein, human; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D020169:Caspases; D004298:Dopamine
keywords: PIMT; Parkinson’s disease; apoptosis; dopamine; oxidative stress; protein l-isoaspartyl (d-aspartyl) methyltransferase