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Betaine Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells

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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.

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Acknowledgments

This research was supported by the “Study of aging-control by energy metabolism based on oriental medicine (K12101)” funded by the “KM-Based Herbal Drug Research Group” of the Korea Institute of Oriental Medicine.

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Correspondence to Mi-Young Lee.

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Im, AR., Kim, YH., Uddin, M.R. et al. Betaine Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells. Cell Mol Neurobiol 33, 625–635 (2013). https://doi.org/10.1007/s10571-013-9921-z

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  • DOI: https://doi.org/10.1007/s10571-013-9921-z

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