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Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with a prevalence of 1–2% in people over the age of 50. Mitochondrial dysfunction occurred in PD patients showing a 15–30% loss of activity in complex I. Asiatic acid (AA), a triterpenoid, is an antioxidant and used for depression treatment, but the effect of AA against PD-like damage has never been reported. In the present study, we investigated the protective effects of AA against H2O2 or rotenone-induced cellular injury and mitochondrial dysfunction in SH-SY5Y cells. Mitochondrial membrane potential (MMP) and the expression of voltage-dependent anion channel (VDAC) were detected with or without AA pretreatment following cellular injury to address the possible mechanisms of AA neuroprotection. The results showed that pre-treatment of AA (0.01–100 nM) protected cells against the toxicity induced by rotenone or H2O2. In addition, MMP dissipation occurred following the exposure of rotenone, which could be prevented by AA treatment. More interestingly, pre-administration of AA inhibited the elevation of VDAC mRNA and protein levels induced by rotenone(100 nM) or H2O2 (300 μM).These data indicate that AA could protect neuronal cells against mitochondrial dysfunctional injury and suggest that AA might be developed as an agent for PD prevention or therapy.

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References

  1. Shastry BS (2001) Parkinson disease: etiology, pathogenesis and future of gene therapy. Neurosci Res 41:5–12. doi:10.1016/S0168-0102(01)00254-1

    Article  PubMed  CAS  Google Scholar 

  2. Yuan H, Zheng JC, Liu P et al (2007) Pathogenesis of Parkinson’s disease: oxidative stress, environmental impact factors and inflammatory processes. Neurosci Bull 23:125–130. doi:10.1007/s12264-007-0018-x

    Article  PubMed  CAS  Google Scholar 

  3. Ramsey CP, Giasson BI (2007) Role of mitochondrial dysfunction in Parkinson’s disease-implications for treatment. Drugs Aging 24:95–105. doi:10.2165/00002512-200724020-00002

    Article  PubMed  CAS  Google Scholar 

  4. Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208:1–25. doi:10.1016/j.expneurol.2007.07.004

    Article  PubMed  CAS  Google Scholar 

  5. Bowling AC, Beal MF (1995) Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci 56:1151–1171. doi:10.1016/0024-3205(95)00055-B

    Article  PubMed  CAS  Google Scholar 

  6. Bindoff LA, Birch-Machin MA, Cartlidge NEF et al (1991) Respiratory chain abnormalities in skeletal muscle from patients with Parkinson’s disease. J Neurol Sci 104:203–208. doi:10.1016/0022-510X(91)90311-T

    Article  PubMed  CAS  Google Scholar 

  7. Blin O, Desnuelle C, Rascol O et al (1994) Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson’s disease and multiple system atrophy. J Neurol Sci 125:95–101. doi:10.1016/0022-510X(94)90248-8

    Article  PubMed  CAS  Google Scholar 

  8. Janetzky B, Hauck S, Youdim MBH et al (1994) Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson’s disease. Neurosci Lett 169:126–128. doi:10.1016/0304-3940(94)90372-7

    Article  PubMed  CAS  Google Scholar 

  9. Benecke R, Strumper P, Weiss H (1993) Electron transfer complexes I and IV of platelets are abnormal in Parkinson’s disease but normal in Parkinson-plus syndromes. Brain 116:1451–1463. doi:10.1093/brain/116.6.1451

    Article  PubMed  Google Scholar 

  10. Cardellach F, Marti MJ, Fernandez-Sola J et al (1993) Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson’s disease. Neurology 43:2170–2172

    Google Scholar 

  11. Cooper JM, Daniel SE, Marsden CD et al (1995) L-dihydroxyphenylalanine and complex I deficiency in Parkinson’s disease brain. Mov Disord 10:295–297. doi:10.1002/mds.870100311

    Article  PubMed  CAS  Google Scholar 

  12. Parker WJ, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26:719–723. doi:10.1002/ana.410260606

    Article  PubMed  Google Scholar 

  13. Armstrong JS (2007) Mitochondrial medicine: Pharmacological targeting of mitochondria in disease. Br J Pharmacol 151:1154–1165. doi:10.1038/sj.bjp.0707288

    Article  PubMed  CAS  Google Scholar 

  14. Liu JK, Ames BN (2005) Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer’s disease, and Parkinson’s disease. Nutr Neurosci 8:67–89. doi:10.1080/10284150500047161

    Article  PubMed  CAS  Google Scholar 

  15. Green D, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629. doi:10.1126/science.1099320

    Article  PubMed  CAS  Google Scholar 

  16. Armstrong JS (2006) The role of the mitochondrial permeability transition in cell death. Mitochondrion 6:225–234. doi:10.1016/j.mito.2006.07.006

    Article  PubMed  CAS  Google Scholar 

  17. Kim J, He L, Qian T et al (2003) Role of the mitochondrial permeability transition in apoptotic and necrotic death after ischemia/reperfusion injury to hepatocytes. Curr Mol Med 3:527–535. doi:10.2174/1566524033479564

    Article  PubMed  CAS  Google Scholar 

  18. Godbole A, Varghese J, Sarin A et al (2003) VDAC is a conserved element of death pathways in plant and animal systems. Biochim Biophys Acta 1642:87–96. doi:10.1016/S0167-4889(03)00102-2

    Article  PubMed  CAS  Google Scholar 

  19. Lemasters JJ, Nieminen AL, Qian T et al (1997) The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury. Mol Cell Biochem 174:159–165. doi:10.1023/A:1006827601337

    Article  PubMed  CAS  Google Scholar 

  20. Zou H, Li Y, Liu X et al (1999) An APAF-1 cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556. doi:10.1074/jbc.274.17.11549

    Article  PubMed  CAS  Google Scholar 

  21. Wang X (2001) The expanding role of mitochondria in apoptosis. Genes Dev 15:2922–2933

    PubMed  CAS  Google Scholar 

  22. Wattanathorn J, Mator L, Muchimapura S et al (2007) Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol 116:325–332. doi:10.1016/j.jep.2007.11.038

    Article  PubMed  Google Scholar 

  23. Shetty BS, Udupa SL, Udupa AL et al (2006) Effect of Centella asiatica L (Umbelliferae) on normal and dexamethasone-suppressed wound healing in Wistar Albino rats. Int J Low Extrem Wounds 5:137–143. doi:10.1177/1534734606291313

    Article  PubMed  Google Scholar 

  24. Gao J, Chen J, Tang XH et al (2006) Mechanism underlying mitochondrial protection of asiatic acid against hepatotoxicity in mice. J Pharm Pharmacol 58:227–233. doi:10.1211/jpp.58.2.0010

    Article  PubMed  CAS  Google Scholar 

  25. Lee Mk, Kim SR, Sung SH et al (2000) Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res Commun Mol Pathol Pharmacol 108:75–86

    PubMed  CAS  Google Scholar 

  26. Mook JI, Shin JE, Yun SH et al (1999) Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity. J Neurosci Res 58:417–425. doi:10.1002/(SICI)1097-4547(19991101)58:3<417::AID-JNR7>3.0.CO;2-G

    Article  Google Scholar 

  27. Betarbet R, Sherer TB, MacKenzie G et al (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306. doi:10.1038/81834

    Article  PubMed  CAS  Google Scholar 

  28. Sherer TB, Betarbet R, Stout AK et al (2002) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22:7006–7015

    PubMed  CAS  Google Scholar 

  29. Kitamura Y, Inden M, Miyamura A et al (2002) Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Neurosci Lett 333:25–28. doi:10.1016/S0304-3940(02)00964-3

    Article  PubMed  CAS  Google Scholar 

  30. Ding HQ, Gao J, Zhu ZR et al (2008) Mitochondrial dysfunction enhances susceptibility to oxidative stress by down-regulation of thioredoxin in human neuroblastoma cells. Neurochem Res 33:43–50. doi:10.1007/s11064-007-9405-y

    Article  PubMed  CAS  Google Scholar 

  31. Wadia J, Chalmers-Redman RM, Ju WJ et al (1998) Mitochondrial membrane potential and nuclear changes in apoptosis caused by serum and nerve growth factor withdrawal: time course and modification by (-)-deprenyl. J Neurosci 18:932–947

    PubMed  CAS  Google Scholar 

  32. Beal MF (1995) Aging, energy, and oxidative stress in neurodegenerative disease. Ann Neurol 38:357–366. doi:10.1002/ana.410380304

    Article  PubMed  CAS  Google Scholar 

  33. Schapira AH, Cooper JM, Dexter D et al (1993) Mitochondrial complex I deficiency in Parkinson’s disease. Adv Neurol 60:288–291

    PubMed  CAS  Google Scholar 

  34. Isenberg JS, Klaunig JE (2000) Role of the mitochondrial membrane permeability transition (MPT) in rotenone-induced apoptosis in liver cells. Toxicol Sci 53:340–351. doi:10.1093/toxsci/53.2.340

    Article  PubMed  CAS  Google Scholar 

  35. Sherer TB, Betarbet R, Testa CM et al (2003) Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 23:10756–10764

    PubMed  CAS  Google Scholar 

  36. Lapointe N, St-Hilaire M, Martinoli MG et al (2004) Rotenone induces non-specific central nervous system and systemic toxicity. FASEB J 18:717–719

    PubMed  CAS  Google Scholar 

  37. Hoglinger GU, Feger J, Prigent A et al (2003) Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 84:491–502. doi:10.1046/j.1471-4159.2003.01533.x

    Article  PubMed  CAS  Google Scholar 

  38. Marella M, Seo BB, Matsuno-Yagi A et al (2007) Mechanism of cell death caused by complex I defects in a rat dopaminergic cell line. J Biol Chem 282:24146–24156. doi:10.1074/jbc.M701819200

    Article  PubMed  CAS  Google Scholar 

  39. Moon Y, Lee KH, Park JH et al (2005) Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q(10). J Neurochem 93:1199–1208. doi:10.1111/j.1471-4159.2005.03112.x

    Article  PubMed  CAS  Google Scholar 

  40. Doran E, Halestrap AP (2000) Cytochrome c release from isolated rat liver mitochondria can occur independently of outer-membrane rupture: possible role of contact sites. Biochem J 348:343–350. doi:10.1042/0264-6021:3480343

    Article  PubMed  CAS  Google Scholar 

  41. Gao J, Tang XH, Dou H et al (2004) Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoids. J Pharm Pharmacol 56:1–7. doi:10.1211/0022357044733

    Article  CAS  Google Scholar 

  42. Lee YS, Jin D-Q, Kwon EJ et al (2002) Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release and enhanced expression of p53 in HepG2 human hepatoma cells. Cancer Lett 186:83–91. doi:10.1016/S0304-3835(02)00260-4

    Article  PubMed  CAS  Google Scholar 

  43. Park BC, Bosire KO, Lee E-S et al (2005) Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells. Cancer Lett 218:81–90. doi:10.1016/j.canlet.2004.06.039

    Article  PubMed  CAS  Google Scholar 

  44. Hsu YL, Kuo PL, Lin LT et al (2005) Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in human breast cancer cells. J Pharmacol Exp Ther 313:333–344. doi:10.1124/jpet.104.078808

    Article  PubMed  CAS  Google Scholar 

  45. Zamzami N, Marchetti P, Castedo M et al (1995) Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 182:367–377. doi:10.1084/jem.182.2.367

    Article  PubMed  CAS  Google Scholar 

  46. Mao Y-R, Jiang L, Duan Y-L et al (2007) Efficacy of catalpol as protectant against oxidative stress and mitochondrial dysfunction on rotenone-induced toxicity in mice brain. Environ Toxicol Pharmacol 23:314–318. doi:10.1016/j.etap.2006.11.012

    Article  CAS  Google Scholar 

  47. Kokoszka JE, Waymire KG, Levy SE et al (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nat Neurosci 427:461–465

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Jiankang Liu, Institute for Brain Aging and Dementia, University of California, Irvine, for his careful reading and editing of this manuscript. This work was supported by Excellent Young Teachers Program of MOE and grants from Jiangsu University (07JDG012).

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Authors and Affiliations

  1. School of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China

    Yuyun Xiong, Minfang Xu & Jing Gao

  2. School of Medicine, Jiangsu University, Zhenjiang, 212013, People’s Republic of China

    Hongqun Ding

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  1. Yuyun Xiong
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Correspondence to Jing Gao.

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Special issue article in honor of Dr. Akitane Mori.

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Xiong, Y., Ding, H., Xu, M. et al. Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells. Neurochem Res 34, 746–754 (2009). https://doi.org/10.1007/s11064-008-9844-0

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