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Detoxified Extract of Rhus verniciflua Stokes Inhibits Rotenone-Induced Apoptosis in Human Dopaminergic Cells, SH-SY5Y

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Abstract

Rhus verniciflua Stokes (RVS), traditionally used as a food supplement and in traditional herbal medicine for centuries in Korea, is known to possess various pharmacological properties. Environmental neurotoxins such as rotenone, a specific inhibitor of complex I provide models of Parkinson’s disease (PD) both in vivo and in vitro. In this study, we investigated the neuroprotective effect of RVS against rotenone-induced toxicity in human dopaminergic cells, SH-SY5Y. Cells exposed to rotenone for 24 h-induced cellular injury and apoptotic cell death. Pretreatment of cells with RVS provided significant protection to SH-SY5Y cells. Further, RVS offered remarkable protection against rotenone-induced oxidative stress and markedly inhibited mitochondrial membrane potential (MMP) disruption. RVS also attenuated the up-regulation of Bax, Caspase-9 and Caspase-3 and down-regulation of Bcl-2. Moreover, pretreatment with RVS prevented the decrease in tyrosine hydroxylase (TH) levels in SH-SY5Y cells. Interestingly, RVS conferred profound protection to human dopaminergic cells by preventing the downregulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). These results suggest that RVS may protect dopaminergic neurons against rotenone-induced apoptosis by multiple functions and contribute to neuroprotection in neurodegenerative diseases, such as PD.

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References

  • Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Canet-Aviles RM, Sherer TB, Mastroberardino PG, McLendon C, Kim JH, Lund S, Na HM, Taylor G, Bence NF, Kopito R, Seo BB, Yagi T, Yagi A, Klinefelter G, Cookson MR, Greenamyre JT (2006) Intersecting pathways to neurodegeneration in Parkinson’s disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiol Dis 22:404–420

    Article  PubMed  CAS  Google Scholar 

  • Borner C (2003) The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol 39:615–647

    Article  PubMed  CAS  Google Scholar 

  • Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 34:279–290

    Article  PubMed  CAS  Google Scholar 

  • Chen LB (1988) Mitochondrial membrane potential in living cells. Annu Rev Cell Biol 4:155–181

    Article  PubMed  CAS  Google Scholar 

  • Chinnaiyan AM, Orth K, O’Rourke K, Duan H, Poirier GG, Dixit VM (1996) Molecular ordering of the cell death pathway-Bcl-2 and Bcl-x (L) function upstream of ced-3-like apoptotic proteases. J Biol Chem 271:4573–4576

    Article  PubMed  CAS  Google Scholar 

  • Cho HS, Kim S, Lee SY, Park JA, Kim SJ, Chun HS (2008) Protective effect of the green tea component l-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology 29:656–662

    Article  PubMed  CAS  Google Scholar 

  • Choi HS, Kim MK, Park HS, Yun SE, Mun SP, Kim JS, Sapkota K, Kim S, Kim TY, Kim SJ (2007) Biological detoxification of lacquer tree (Rhus verniciflua Stokes) stem bark by mushroom species. Food Sci Biotechnol 16:935–942

    CAS  Google Scholar 

  • Dunnett SB, Bjorklund A (1999) Prospects for new restorative and neuroprotective treatments in Parkinson’s disease. Nature 399:A32–A39

    Article  PubMed  CAS  Google Scholar 

  • Evans JR, Barker RA (2008) Nurotrophic factors as a therapeutic target for Parkinson’s disease. Expert Opin Ther Targets 12:437–447

    Article  PubMed  CAS  Google Scholar 

  • Gandhi S, Wood NW (2005) Molecular pathogenesis of Parkinson’s disease. Hum Mol Genet 14:2749–2755

    Article  Google Scholar 

  • Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112

    Article  PubMed  CAS  Google Scholar 

  • Hefti F (1997) Pharmacology of neurotrophic factors. Annu Rev Pharmacol Toxicol 37:239–267

    Article  PubMed  CAS  Google Scholar 

  • Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  PubMed  CAS  Google Scholar 

  • Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53:S26–S38

    Article  PubMed  CAS  Google Scholar 

  • Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47:161–170

    Google Scholar 

  • Kim TJ (1996) In Korea resource plants, vol 2. Seoul National University Press, Seoul, Korea, pp 292–297

    Google Scholar 

  • Kim IT, Park YM, Shin KM, Ha J, Choi J, Jung HJ, Park HJ, Lee KT (2004) Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, Pueraria thenbergiana and Rhus verniciflua. J Ethnopharmacol 94:165–173

    Article  PubMed  Google Scholar 

  • Kim JH, Go HY, Jin DH, Kim HP, Hong MH, Chung WY, Park JH, Jang JB, Jung H, Shin YC, Kim SH, Ko SG (2008) Inhibition of the PI3K-Akt/PKB survival pathway enhanced an ethanol extract of Rhus verniciflua Stokes-induced apoptosis via a mitochondrial pathway in AGS gastric cancer cell lines. Cancer Lett 265:197–205

    Article  PubMed  CAS  Google Scholar 

  • Kitts DD, Lim KT (2001) Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS). J Toxicol Environ Health A 64:357–371

    Article  PubMed  CAS  Google Scholar 

  • Lang AE (2006) Neuroprotection in Parkinson’s disease: and now for something completely different? Lancet Neurol 5:990–991

    Article  PubMed  Google Scholar 

  • Lee JC, Kim J, Lim KT, Yang MS, Jang YS (2001) Ethanol eluted extract of Rhus verniciflua Stokes showed both antioxidant and cytotoxic effects on mouse thymocytes depending on the dose and time of the treatment. J Biochem Mol Biol 34:250–258

    CAS  Google Scholar 

  • Lee SH, Choi WC, Yoon SW (2009) Impact of standardized Rhus verniciflua stokes extract as complementary therapy on metastatic colorectal cancer: a Korean single-center experience. Integr Cancer Ther 8:148–152

    Article  PubMed  Google Scholar 

  • Licker V, Kövari E, Hochstrasser DF, Burkhard PR (2009) Proteomics in human Parkinson’s disease research. J Proteomics 73:10–29

    Article  PubMed  CAS  Google Scholar 

  • Lim KT, Hu C, Kitts DD (2001) Antioxidant activity of a Rhus verniciflua Stokes ethanol extract. Food Chem Toxicol 39:229–237

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Toledano MA, Redondo C, Lobo MV, Reimers D, Herranz AS, Paino CL, Bazan E (2004) Tyrosine hydroxylase induction by basic fibroblast growth factor and cyclic AMP analogs in striatal neural stem cells: role of ERK1/ERK2 mitogen-activated protein kinase and protein kinase C. J Histochem Cytochem 52:1177–1189

    Article  PubMed  CAS  Google Scholar 

  • Maruyama W, Nitta A, Shamoto-Nagai M, Hirata Y, Akao Y, Youdim MBH, Furukawa S, Nabeshima T, Naoi M (2004) N-propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor. Neurochem Int 44:393–400

    Article  PubMed  CAS  Google Scholar 

  • Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 28:57–87

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T (1992) Molecular biology of dopamine systems. In: Rinne UK, Yanagisawa N (eds) Controversies in the treatment of Parkinson’s disease’. PMSI, Tokyo, pp 15–26

    Google Scholar 

  • Nagatsu T (1995) Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Essays Biochem 30:15–35

    PubMed  CAS  Google Scholar 

  • Nagatsu T, Levitt M, Undenfriend S (1964) Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis. J Biol Chem 239:2910–2917

    PubMed  CAS  Google Scholar 

  • Olanow CW, Kieburtz K, Schapira AH (2008) Why have we failed to achieve neuroprotection in Parkinson’s disease? Ann Neurol 2:S101–S110

    Google Scholar 

  • Omata N, Murata T, Takamatsu S, Maruoka N, Mitsuya H, Yonekura Y, Fujibayashi Y, Wada Y (2008) Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatment. Bipolar Disord 10:360–368

    Article  PubMed  CAS  Google Scholar 

  • Panov A, Dikalov S, Shalbuyeva N, Taylor G, Sherer T, Greenamyre JT (2005) Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. J Biol Chem 280:42026–42035

    Article  PubMed  CAS  Google Scholar 

  • Park KY, Jung GO, Lee KT, Choi JW, Choi MY, Kim GT, Jung JJ, Park HJ (2004) Antimutagenic activity of flavonoids from the heartwood of Rhus verniciflua. J Ethnopharmacol 90:73–79

    Article  PubMed  CAS  Google Scholar 

  • Park BC, Lee YS, Park HJ, Kwak MK, Yoo BK, Kim JY, Kim JA (2007) Protective effects of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-hydroxydopamine-induced neuronal cell death. Exp Mol Med 39:316–326

    PubMed  CAS  Google Scholar 

  • Prehn JH, Bindokas VP, Jordán J, Galindo MF, Ghadge GD, Roos RP, Boise LH, Thompson CB, Krajewski S, Reed JC, Miller RJ (1996) Protective effect of transforming growth factor-beta 1 on beta-amyloid neurotoxicity in rat hippocampal neurons. Mol Pharmacol 49:319–328

    PubMed  CAS  Google Scholar 

  • Radad K, Rausch WD, Gille G (2006) Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochem Int 49:379–386

    Article  PubMed  CAS  Google Scholar 

  • Rahn CA, Bombick DW, Doolittle DJ (1991) Assessment of mitochondrial membrane potential as an indicator of cytotoxicity. Fundam Appl Toxicol 16:435–448

    Article  PubMed  CAS  Google Scholar 

  • Saavedra A, Baltazar G, Duarte EP (2008) Driving GDNF expression: the green and the red traffic lights. Prog Nurobiol 86:186–215

    Article  CAS  Google Scholar 

  • Sapkota K, Kim S, Kim JS, Kim MK, Chun HS, Kim SJ (2009) Effects of the detoxified extract of Rhus verniciflua on regulation of catecholamine biosynthesis. J Korean Soc Appl Biol Chem 52:590–599

    Article  Google Scholar 

  • Sherer TB, Kim JH, Betarbet R, Greenamyre JT (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 179:9–16

    Article  PubMed  CAS  Google Scholar 

  • Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT (2007) Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem 100:1469–1479

    PubMed  CAS  Google Scholar 

  • Testa CM, Sherer TB, Greenamyre JT (2005) Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Brain Res Mol Brain Res 134:109–118

    Article  PubMed  CAS  Google Scholar 

  • Theofilopoulos S, Goggi J, Riaz SS, Jauniaux E, Stern GM, Bradford HF (2001) Parallel induction of the formation of dopamine and its metabolites with induction of tyrosine hydroxylase expression in foetal rat and human cerebral cortical cells by brain-derived neurotrophic factor and glial-cell derived neurotrophic factor. Brain Res Dev Brain Res 127:111–122

    Article  PubMed  CAS  Google Scholar 

  • Ubl JJ, Chatton JY, Chen S et al (1996) A critical evaluation of in situ measurement of mitochondrial electrical potentials in single hepatocytes. Biochem Biophys Acta 1276:124–132

    Article  PubMed  Google Scholar 

  • Yang D, Peng C, Li X, Fan X, Li L, Ming M, Chen S, Le W (2008) Pitx3-transfected astrocytes secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and protect dopamine neurons in mesencephalon cultures. J Neurosci Res 86:3393–3400

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant (Code: 20080701034003) from the BioGreen 21 Program, Rural Development Administration, Republic of Korea.

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Authors and Affiliations

  1. Department of Biotechnology, Chosun University, 375 Seosuk-dong, Dong-gu, Gwang-ju, 501-759, Republic of Korea

    Kumar Sapkota, Se-Eun Park & Sung-Jun Kim

  2. Department of Alternative medicine, Gwangju University, Gwangju, 503-703, Republic of Korea

    Seung Kim

  3. Central Department of Zoology, Tribhuvan University, Kirtipur, Kathmandu, Nepal

    Kumar Sapkota

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  1. Kumar Sapkota
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  4. Sung-Jun Kim
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Correspondence to Sung-Jun Kim.

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Kumar Sapkota and Seung Kim contributed equally to this study.

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Sapkota, K., Kim, S., Park, SE. et al. Detoxified Extract of Rhus verniciflua Stokes Inhibits Rotenone-Induced Apoptosis in Human Dopaminergic Cells, SH-SY5Y. Cell Mol Neurobiol 31, 213–223 (2011). https://doi.org/10.1007/s10571-010-9609-6

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