title: Betaine protects against rotenone-induced neurotoxicity in PC12 cells.
abstract: Rotenone is an inhibitor of mitochondrial complex I-induced neurotoxicity in PC12 cells and has been widely studied to elucidate the pathogenesis of Parkinson's disease. We investigated the neuroprotective effects of betaine on rotenone-induced neurotoxicity in PC12 cells. Betaine inhibited rotenone-induced apoptosis in a dose-dependent manner, with cell viability increasing from 50 % with rotenone treatment alone to 71 % with rotenone plus 100-μM betaine treatment. Flow cytometric analysis demonstrated cell death in the rotenone-treated cells to be over 50 %; the number of live cells increased with betaine pretreatment. Betaine pretreatment of PC12 cells attenuated rotenone-mediated mitochondrial dysfunction, including nuclear fragmentation, ATP depletion, mitochondrial membrane depolarization, caspase-3/7 activation, and reactive oxygen species production. Western blots demonstrated activation of caspase-3 and caspase-9, and their increased expression levels in rotenone-treated cells; betaine decreased caspase-3 and caspase-9 expression levels and suppressed their activation. Together, these results suggest that betaine may serve as a neuroprotective agent in the treatment of neurodegenerative diseases.
authors.affiliation: KM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon, Korea.
authors.forename: A-Rang
authors.initials: AR
authors.lastname: Im
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Md Romij
authors.initials: MR
authors.lastname: Uddin
authors.forename: Sungwook
authors.initials: S
authors.lastname: Chae
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D012402:Rotenone / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D012402:Rotenone; D013481:Superoxides; D001622:Betaine; D020169:Caspases