title: TRPC1 protects dopaminergic SH-SY5Y cells from MPP+, salsolinol, and N-methyl-(R)-salsolinol-induced cytotoxicity.
abstract: Neurotoxins and alterations in Ca2+ homeostasis have been associated with Parkinson's disease (PD), but the role of store-operated Ca2+ entry channels is not well understood. Previous studies have shown the neurotoxicity of salsolinol and 1-methyl-4-phenylpyridinium ion on SH-SY5Y cells and cytoprotection induced by transient receptor potential protein 1 (TRPC1). In the present study, N-methyl-(R)-salsolinol was tested for its cellular toxicity and effects on TRPC1 expression. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, DAPI (4',6-diamidino-2-phenylindole), fluorescein isothiocyanate-Annexin-V/propidium iodide, western blot analysis, and JC-1 labeling revealed that the three indicated drugs could induce caspase-dependent, mitochondrial-mediated apoptosis. Exposure of SH-SY5Y cells to the indicated drugs resulted in a significant decrease in thapsigargin-mediated Ca2+ influx and TRPC1 expression. Immunocytochemistry experiments revealed that neurotoxins treatment induced TRPC1 translocation to the cytoplasm. Taken together, our results indicate that treatment with neurotoxins may alter Ca2+ homeostasis and induce mitochondrial-mediated caspase-dependent cytotoxicity, an important characteristic of PD.
authors.affiliation: Cell Biology Laboratory, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Abida
authors.initials: A
authors.lastname: Arshad
authors.forename: Xuechai
authors.initials: X
authors.lastname: Chen
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Cong
authors.forename: Hong
authors.initials: H
authors.lastname: Qing
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D012490:Salsoline Alkaloids / Q000633:toxicity*; D050052:TRPC Cation Channels / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D009498:Neurotoxins; D012490:Salsoline Alkaloids; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C036617:salsolinol; C032837:salsoline; D020169:Caspases; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium
keywords: N-methyl-(R)-salsolinol; Parkinson's disease; SH-SY5Y cell; TRPC1; calcium channel; neurotoxin