Betaine Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells
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.
KeywordsApoptosis Betaine Mitochondrial dysfunction Neuroprotection Rotenone
- Moran M, Rivera H, Sanchez-Arago M, Blazquez A, Merinero B, Ugalde C, Arenas J, Cuezva JM, Martin MA (2010) Mitochondrial bioenergetics and dynamics interplay in complex I-deficient fibroblasts. Biochim Biophys Acta 802:443–453Google Scholar
- Wei HL, Jiafeng S, Ming C, Hongyan C, Linsen H (2008) Mechanisms of rotenone-induced neurotoxicity in PC 12 cells. Neural Regen Res 3:1281–1285Google Scholar