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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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References

  • Batandier C, Fontaine E, Keriel C, Leverve XM (2002) Determination of mitochondrial reactive oxygen species: methodological aspects. J Cell Mol Med 6:175–187

    Article  PubMed  CAS  Google Scholar 

  • Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G (2007) Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. BMC Cardiovasc Disord 7:20

    Article  PubMed  Google Scholar 

  • Caserta MT, Bannon Y, Fernandez F, Giunta B, Schoenberg MR, Tan J (2009) Chapter 1 Normal brain aging: clinical, immunological, neuropsychological, and neuroimaging features. Int Rev Neurobiol 84:1–19

    Article  PubMed  Google Scholar 

  • Cave M, Deaciuc I, Mendez C, Song Z, Joshi-Barve S, Barve S, McClain C (2007) Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem 18:184–195

    Article  PubMed  CAS  Google Scholar 

  • Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80:539–549

    PubMed  CAS  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  PubMed  CAS  Google Scholar 

  • Du YP, Peng JS, Sun A, Tang ZH, Ling WH, Zhu HL (2009) Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model. BMC Cancer 9:261

    Article  PubMed  Google Scholar 

  • Fukae J, Mizuno Y, Hattori N (2007) Mitochondrial dysfunction in Parkinson’s disease. Mitochondrion 7:58–62

    Article  PubMed  CAS  Google Scholar 

  • Ganesan B, Anandan R (2009) Protective effect of betaine on changes in the levels of lysosomal enzyme activities in heart tissue in isoprenaline-induced myocardial infarction in Wistar rats. Cell Stress Chaperones 14:661–667

    Article  PubMed  CAS  Google Scholar 

  • Ganesan B, Anandan R, Lakshmanan PT (2011) Studies on the protective effects of betaine against oxidative damage during experimentally induced restraint stress in Wistar albino rats. Cell Stress Chaperones 16:641–652

    Article  PubMed  CAS  Google Scholar 

  • Ho YS, So KF, Chang RC (2010) Anti-aging herbal medicine–how and why can they be used in aging-associated neurodegenerative diseases? Ageing Res Rev 9:354–362

    Article  PubMed  Google Scholar 

  • Kanbak G, Inal M, Baycu C (2001) Ethanol-induced hepatotoxicity and protective effect of betaine. Cell Biochem Funct 19:281–285

    Article  PubMed  CAS  Google Scholar 

  • Keane PC, Kurzawa M, Blain PG, Morris CM (2011) Mitochondrial dysfunction in Parkinson’s disease. Parkinsons Dis 2011:716871

    PubMed  CAS  Google Scholar 

  • Kirkinezos IG, Moraes CT (2001) Reactive oxygen species and mitochondrial diseases. Semin Cell Dev Biol 12:449–457

    Article  PubMed  CAS  Google Scholar 

  • Martin LJ (2010) Mitochondrial and cell death mechanisms in neurodegenerative diseases. Pharmaceuticals (Basel) 3:839–915

    Article  CAS  Google Scholar 

  • Mehler MF, Gokhan S (2000) Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat. Trends Neurosci 23:599–605

    Article  PubMed  CAS  Google Scholar 

  • 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 802:443–453

    Google Scholar 

  • Pettmann B, Henderson CE (1998) Neuronal cell death. Neuron 20:633–647

    Article  PubMed  CAS  Google Scholar 

  • Petty RD, Sutherland LA, Hunter EM, Cree IA (1995) Comparison of MTT and ATP based assays for the measurement of viable cell number. J Biolumin Chemilumin 10:29–34

    Article  PubMed  CAS  Google Scholar 

  • Ribe EM, Serrano-Saiz E, Akpan N, Troy CM (2008) Mechanisms of neuronal death in disease: defining the models and the players. Biochem J 415:165–182

    Article  PubMed  CAS  Google Scholar 

  • Riederer BM, Leuba G, Vernay A, Riederer IM (2011) The role of the ubiquitin proteasome system in Alzheimer’s disease. Exp Biol Med (Maywood) 236:268–276

    Article  CAS  Google Scholar 

  • Samantaray S, Knaryan VH, Guyton MK, Matzelle DD, Ray SK, Banik NL (2007) The parkinsonian neurotoxin rotenone activates calpain and caspase-3 leading to motoneuron degeneration in spinal cord of Lewis rats. Neuroscience 146:741–755

    Article  PubMed  CAS  Google Scholar 

  • Shin YG, Cho KH, Kim JM, Park MK, Park JH (1999) Determination of betaine in Lycium chinense fruits by liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr A 857:331–335

    Article  PubMed  CAS  Google Scholar 

  • Tenenbaum L, Chtarto A, Lehtonen E, Blum D, Baekelandt V, Velu T, Brotchi J, Levivier M (2002) Neuroprotective gene therapy for Parkinson’s disease. Curr Gene Ther 2:451–483

    Article  PubMed  CAS  Google Scholar 

  • Velier JJ, Ellison JA, Kikly KK, Spera PA, Barone FC, Feuerstein GZ (1999) Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat. J Neurosci 19:5932–5941

    PubMed  CAS  Google Scholar 

  • Vila M, Ramonet D, Perier C (2008) Mitochondrial alterations in Parkinson’s disease: new clues. J Neurochem 107:317–328

    Article  PubMed  CAS  Google Scholar 

  • Wei HL, Jiafeng S, Ming C, Hongyan C, Linsen H (2008) Mechanisms of rotenone-induced neurotoxicity in PC 12 cells. Neural Regen Res 3:1281–1285

    Google Scholar 

  • Weir HJ, Murray TK, Kehoe PG, Love S, Verdin EM, O’Neill MJ, Lane JD, Balthasar N (2012) CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer’s disease. PLoS One 7:e48225

    Article  PubMed  CAS  Google Scholar 

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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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Authors and Affiliations

  1. KM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, 461-24, Jeonmin-dong, Yuseong-gu, Daejeon, 305-811, Korea

    A-Rang Im, Young-Hwa Kim, Md. Romij Uddin, Sungwook Chae, Hye Won Lee, Yun Hee Kim & Mi-Young Lee

  2. Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-742, Korea

    Yeong Shik Kim

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  1. A-Rang Im
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  2. Young-Hwa Kim
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  4. Sungwook Chae
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  5. Hye Won Lee
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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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