Cellular and Molecular Neurobiology

, Volume 33, Issue 5, pp 625–635 | Cite as

Betaine Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells

  • A-Rang Im
  • Young-Hwa Kim
  • Md. Romij Uddin
  • Sungwook Chae
  • Hye Won Lee
  • Yun Hee Kim
  • Yeong Shik Kim
  • Mi-Young Lee
Original Research

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.

Keywords

Apoptosis Betaine Mitochondrial dysfunction Neuroprotection Rotenone 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • A-Rang Im
    • 1
  • Young-Hwa Kim
    • 1
  • Md. Romij Uddin
    • 1
  • Sungwook Chae
    • 1
  • Hye Won Lee
    • 1
  • Yun Hee Kim
    • 1
  • Yeong Shik Kim
    • 2
  • Mi-Young Lee
    • 1
  1. 1.KM-Based Herbal Drug Research GroupKorea Institute of Oriental MedicineDaejeonKorea
  2. 2.Natural Products Research Institute, College of PharmacySeoul National UniversitySeoulKorea

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