Curcumin protects against rotenone-induced neurotoxicity in cell and drosophila models of Parkinson’s disease

Zhaohui Liu, Tianxia Li, Dejun Yang, Wanli W. Smith

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, USA.

DOI: 10.4236/apd.2013.21004                

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder resulting from a selective loss of dopaminergic neurons. The pathogenesis of PD remains incompletely understood, but increasing evidence from human and animal studies has suggested that oxidative damage contributes to the neuronal loss in PD. In this study, we used rotenone (a mitochondrial complex I inhibitor) based cell and Drosophila models that resemble some key pathological features of PD to test whether curcumin, a potent antioxidant compound, derived from the curry spice turmeric, could protect against rotenone-induced neuronal toxicity. We found that curcumin reduced rotenone induced cell death in SH-SY5Y human neuroblastoma cells and alleviated PD-like symptoms in drosophila via reducing the intracellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting the caspase-3/caspase-9 activity. These results suggest that curcumin is a promising therapeutic compound for PD.

Keywords

Parkinson’s Disease; Curcumin; Rotenone; Reactive Oxygen Species; Mitochondria; Drosophila

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Dawson, T.M., Dawson, V.L. (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science, 302, 819-822. doi:10.1126/science.1087753
[2]	Ross, C.A., Smith, W.W. (2007) Gene-environment in- teractions in Parkinson’s disease. Parkinsonism & Re- lated Disorders, 13, S309-S315. doi:10.1016/S1353-8020(08)70022-1
[3]	Dick, F.D. (2006) Parkinson’s disease and pesticide ex- posures. British Medical Bulletin, 79-80, 219-231. doi:10.1093/bmb/ldl018
[4]	Hoglinger, G.U., Oertel, W.H. and Hirsch, E.C. (2006) The rotenone model of parkinsonism—The five years in- spection. Journal of Neural Transmission, 70, 269-272. doi:10.1007/978-3-211-45295-0_41
[5]	Sherer, T.B., Betarbet, R., Stout, A.K., Lund, S., Baptista, M., Panov, A.V., Cookson, M.R. and Greenamyre, J.T. (2002) An in vitro model of Parkinson’s disease: Linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. The Journal of Neuro- science, 22, 7006-7015.
[6]	Betarbet, R., Canet-Aviles, R.M., Sherer, T.B., Mastro- berardino, P.G., McLendon, C., Kim, J.H., Lund, S., Na, H.M., Taylor, G. and Bence, N.F. (2006) Intersecting pathways to neurodegeneration in Parkinson’s disease: Effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiology of Disease, 22, 404-420. doi:10.1016/j.nbd.2005.12.003
[7]	Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V. and Greenamyre, J.T. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nature Neuroscience, 3, 1301-1306. doi:10.1038/81834
[8]	Coulom, H. and Birman, S. (2004) Chronic exposure to ro- tenone models sporadic Parkinson’s disease in Drosophila melanogaster. The Journal of Neuroscience, 24, 10993-10998. doi:10.1523/JNEUROSCI.2993-04.2004
[9]	Hosamani, R., Ramesh, S.R. and Muralidhara. (2010) Attenuation of rotenone-induced mitochondrial oxidative damage and neurotoxicty in Drosophila melanogaster supplemented with creatine. Neurochemical Research, 35, 1402-1412. doi:10.1007/s11064-010-0198-z
[10]	Kelloff, G.J., Crowell, J.A., Steele, V.E., Lubet, R.A., Malone, W.A., Boone, C.W., Kopelovich, L., Hawk, E.T., Lieberman, R. and Lawrence, J.A. (2000) Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. The Journal of Nutrition, 130, 467S-471S.
[11]	Zhao, B.L., Li, X.J., He, R.G., Cheng, S.J. and Xin, W.J. (1989) Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Bio- physics, 14, 175-185.
[12]	Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G. and Frautschy, S.A. (2005) Curcumin inhibits for- mation of amyloid beta oligomers and fibrils, binds pla- ques, and reduces amyloid in vivo. The Journal of Bio- logical Chemistry, 280, 5892-5901. doi:10.1074/jbc.M404751200
[13]	Lim, G.P., Chu, T., Yang, F., Beech, W., Frautschy, S.A. and Cole, G.M. (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. The Journal of Neuroscience, 21, 8370- 8377.
[14]	Smith, W.W., Jiang, H., Pei, Z., Tanaka, Y., Morita, H., Sawa, A., Dawson, V.L., Dawson, T.M. and Ross, C.A. (2005) Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synu- clein-induced toxicity. Human Molecular Genetics, 14, 3801-3811. doi:10.1093/hmg/ddi396
[15]	Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., Moran, T. and Smith, W.W. (2008) A Drosophila model for LRRK2-linked parkinsonism. Proceedings of the National Academy of Sciences of United States of America, 105, 2693-2698. doi:10.1073/pnas.0708452105
[16]	Liu, Z., Celotto, A.M., Romero, G., Wipf, P. and Palladino, M.J. (2011) Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial dis- ease pathogenesis. Neurobiology of Disease, 45, 362-368. doi:10.1016/j.nbd.2011.08.022
[17]	Ahmadi, F.A., Linseman, D.A., Grammatopoulos, T.N., Jones, S.M., Bouchard, R.J., Freed, C.R., Heidenreich, K.A. and Zawada, W.M. (2003) The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesen- cephalic dopaminergic neurons. Journal of Neurochemis- try, 87, 914-921. doi:10.1046/j.1471-4159.2003.02068.x
[18]	Newhouse, K., Hsuan, S.L., Chang, S.H., Cai, B., Wang, Y. and Xia, Z. (2004) Rotenone-induced apoptosis is me- diated by p38 and JNK MAP kinases in human dopa- minergic SH-SY5Y cells. Society of Toxicology, 79, 137- 146. doi:10.1093/toxsci/kfh089
[19]	Ramachandiran, S., Hansen, J.M., Jones, D.P., Richard- son, J.R. and Miller, G.W. (2007) Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: Oxidation of thioredoxin and caspase-3 activation. Society of Toxico- logy, 95, 163-171. doi:10.1093/toxsci/kfl125
[20]	Leung, K.W., Yung, K.K., Mak, N.K., Chan, Y.S., Fan, T.P. and Wong, R.N. (2007) Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rote- none toxicity. Neuropharmacology, 52, 827-835. doi:10.1016/j.neuropharm.2006.10.001
[21]	Dexter, D.T., Carter, C.J., Wells, F.R., Javoy-Agid, F., Agid, Y., Lees, A., Jenner, P. and Marsden, C.D. (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. Journal of Neurochemistry, 52, 381- 389. doi:10.1111/j.1471-4159.1989.tb09133.x
[22]	Sian, J., Dexter, D.T., Lees, A.J., Daniel, S., Agid, Y., Javoy-Agid, F., Jenner, P. and Marsden, C.D. (1994) Al- terations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Annals of Neurology, 36, 348-355. doi:10.1002/ana.410360305
[23]	Giasson, B.I., Duda, J.E., Murray, I.V., Chen, Q., Souza, J.M., Hurtig, H.I., Ischiropoulos, H., Trojanowski, J.Q. and Lee, V.M. (2000) Oxidative damage linked to neu- rodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science, 290, 985-989. doi:10.1126/science.290.5493.985
[24]	Tabner, B.J., Turnbull, S., El-Agnaf, O.M. and Allsop, D. (2002) Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Par- kinson’s disease. Free Radical Biology and Medicine 32, 1076-1083. doi:10.1016/S0891-5849(02)00801-8
[25]	Maguire-Zeiss, K.A., Short, D.W. and Federoff, H.J. (2005) Synuclein, dopamine and oxidative stress: Co-con- spirators in Parkinson’s disease? Molecular Brain Re- search, 134, 18-23. doi:10.1016/j.molbrainres.2004.09.014
[26]	Alam, Z.I., Jenner, A., Daniel, S.E., Lees, A.J., Cairns, N., Marsden, C.D., Jenner, P. and Halliwell, B. (1997) Oxida- tive DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substan- tia nigra. Journal of Neurochemistry, 69, 1196-1203. doi:10.1046/j.1471-4159.1997.69031196.x
[27]	Alam, Z.I., Daniel, S.E., Lees, A.J., Marsden, D.C., Jenner, P. and Halliwell, B. (1997) A generalised increase in protein carbonyls in the brain in Parkinson’s but not in- cidental Lewy body disease. Journal of Neurochemistry, 69, 1326- 1329. doi:10.1046/j.1471-4159.1997.69031326.x
[28]	Hasegawa, E., Takeshige, K., Oishi, T., Murai, Y. and Minakami, S. (1990) 1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. Biochemical and Bio- physical Research Communications, 170, 1049-1055. doi:10.1016/0006-291X(90)90498-C
[29]	Lotharius, J. and O’Malley, K.L. (2000) The parkinson- ism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity. The Journal of Biological Chemistry, 275, 38581- 38588. doi:10.1074/jbc.M005385200
[30]	Cassarino, D.S., Fall, C.P., Swerdlow, R.H., Smith, T.S., Halvorsen, E.M., Miller, S.W., Parks, J.P., Parker, W.D., Jr. and Bennett, J.P., Jr. (1997) Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson’s disease. Biochimica et Biophysica Acta, 1362, 77-86. doi:10.1016/S0925-4439(97)00070-7
[31]	Votyakova, T.V. and Reynolds, I.J. (2001) DeltaPsi(m)- Dependent and -independent production of reactive oxygen species by rat brain mitochondria. Journal of Neuro- chemistry, 79, 266-277. doi:10.1046/j.1471-4159.2001.00548.x
[32]	Hensley, K., Pye, Q.N., Maidt, M.L., Stewart, C.A., Rob- inson, K.A., Jaffrey, F. and Floyd, R.A. (1998) Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative elec- tron acceptors with complex I indicates a substrate reduc- tion site upstream from the rotenone binding site. Journal of Neurochemistry, 71, 2549-2557. doi:10.1046/j.1471-4159.1998.71062549.x
[33]	Martin-Aragon, S., Benedi, J.M. and Villar, A.M. (1997) Modifications on antioxidant capacity and lipid peroxida- tion in mice under fraxetin treatment. Journal of Phar- macy and Pharmacology, 49, 49-52. doi:10.1111/j.2042-7158.1997.tb06751.x
[34]	Sreejayan and Rao, M.N. (1997) Nitric oxide scavenging by curcuminoids. Journal of Pharmacy and Pharmacology, 49, 105-107. doi:10.1111/j.2042-7158.1997.tb06761.x
[35]	Liu, Z., Yu, Y., Li, X., Ross, C.A. and Smith, W.W. (2011) Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacological Research, 63, 439-444. doi:10.1016/j.phrs.2011.01.004
[36]	Yang, D., Li, T., Liu, Z., Arbez, N., Yan, J., Moran, T.H., Ross, C.A. and Smith, W.W. (2012) LRRK2 kinase acti- vity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: Suppression by curcumin. Neurobiology of Disease, 47, 385-392. doi:10.1016/j.nbd.2012.05.020
[37]	Wang, X., Qin, Z.H., Leng, Y., Wang, Y., Jin, X., Chase, T.N. and Bennett, M.C. (2002) Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells. Journal of Neurochemistry, 83, 1094-1102. doi:10.1046/j.1471-4159.2002.01224.x
[38]	Chainani-Wu, N. (2003) Safety and anti-inflammatory activity of curcumin: A component of tumeric (Curcuma longa). Journal of Alternative and Complementary Medi- cine, 9, 161-168. doi:10.1089/107555303321223035
[39]	Sharm,a R.A., Euden, S.A., Platton, S.L., Cooke, D.N., Shafayat, A., Hewitt, H.R., Marczylo, T.H., Morgan, B., Hemingway, D. and Plummer, S.M. (2004) Phase I clini- cal trial of oral curcumin: Biomarkers of systemic activity and compliance. Clinical Cancer Research, 10, 6847- 6854.
[40]	Hsu, C.H. and Cheng, A.L. (2007) Clinical studies with curcumin. Advances in Experimental Medicine and Bio- logy, 595, 471-480. doi:10.1007/978-0-387-46401-5_21