Paraquat-induced Neuronal Apoptosis Associated with Parkinson's Disease

Abstract

Abstract:Parkinson’s disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra (SN); however, the causes of PD remain unknown. Over the years the etiologic involvement of genetic inheritance versus environmental exposures has been under debate. In this sense, a lack of evidence for heritability of the idiopathic PD has pointed to environmental risk factors as potential contributors to the disease etiology. It is reported that, Paraquat (PQ) (1,1-dimethyl-4,4′-bipyridinium dichloride), a widely used herbicide, was suggested as a potential etiologic factor for the development of PD. Paraquat is structurally similar to the neurotoxin MPP+ (1-methyl-4-phenylpyridinium), the latter being an active metabolite derived from MPTP (1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and being capable of inducing the apoptosis of neural cells. In this paper, we used the model of PQ induced toxicity on SH-SY5Y to study the mechanism underlying its effect in causing dopaminergic cells degeneration and necrosis. To this end, we determined whether PQ activated apoptotic pathways leading to the pathogenesis of PD as MPP+ does, or caused intracellular oxidative stress， mitochondrial dysfunction or proteasome abnormality to induce PD. Intensive study of the molecular mechanisms for PQ induction of PD will be of great value for the prevention and treatment of PD.

Key words:Parkinson&,rsquo,s disease,Paraquat,apoptosis

CLC Number:

R742，R964

TIAN Xiao-fei, LI Jian-feng, PANG Hao. Paraquat-induced Neuronal Apoptosis Associated with Parkinson's Disease[J]. Acta Neuropharmacologica, 2011, 1(5): 27-33.

References

[1] Matthew James Farrer. Genetics of Parkinson disease: paradigm shifts and future prospects [J]. Nat Rev Genet, 2006,7(4):306-318.

[2] Robert E. Burke. Programmed cell death and Parkinson’s disease[J]. Movement Disorders, 1998, 13(Suppl 1):17-23.

[3] James Parkinson. An essay on the shaking palsy[J]. J Neuropsychiatry Clin Neurosci, 2002, 14(2):223-236.

[4] Christine Klein, Michael G Schlossmacher. The genetics of Parkinson disease: Implications for neurological care[J]. Nat Clin Pract Neurol, 2006, 2(3): 136-146.

[5] Caroline M. Tanner, Ruth Ottman, Samuel M. Goldman, et al. Parkinson disease in twins: an etiologic study[J]. JAMA, 1999, 281(4):341-346.

[6] Rosa A González-Polo, Andrea Rodríguez-Martín, Jose M Morán, et al. Paraquat-induced apoptotic cell death in cerebellar granule cells[J]. Brain Res, 2004, 1011(2):170-176.

[7] Rose A González-Polo, Mireia Niso-Santano, Miguel A Ortíz-Ortíz, et al. Inhibition of paraquat-induced autophagy accelerates the apoptotic cell death in neuroblastoma SH-SY5Y cells[J]. Toxicol Sci, 2007, 97(2):448-458.

[8] Jonathan A Javitch, Robert J D'Amato, Stephen M Strittmatter, et al. Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity[J]. Proc Natl Acad Sci USA, 1985, 82(7):2173-2177.

[9] Sai Takafumi, Uchida Kazuyuki, Nakayama Hiroyuki. Acute toxicity of MPTP and MPP(+) in the brain of embryo and newborn mice[J]. Exp Toxicol Pathol, 2011, 65(1-2):113-119.

[10] Chade A R, Kasten M, Tanner C M. Nongenetic causes of Parkinson’s disease[J]. J Neural Transm Suppl, 2006, (70):147-151.

[11] James S Bus, James E Gibson. Paraquat: model for oxidant-initiated toxicity[J]. Environ Health Perspect, 1984, 55:37-46.

[12] Shimizu K, Matsubara K, Ohtaki K, et al. Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats[J]. Brain Res, 2003, 976 (2):243–252.

[13] Xie Hong-rong, Hu Lin-sen, Li Guo-yi. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease[J]. Chin Med J (Engl), 2010, 123(8):1086-1092.

[14] James S Bus, James E Gibson. Paraquat: model for oxidant-initiated toxicity[J]. Environ Health Perspect, 1984 ,55:37-46.

[15] Zacharias E Suntres. Role of antioxidants in paraquat toxicity[J]. Toxicology, 2002, 180(1):65-77.

[16] Dodge AD. The mode of action of the bipyridylium herbicides, paraquat and diquat[J]. Endeavour, 1971, 30(111):130-135.

[17] Cappelletti G, Maggioni MG, Maci R. Apoptosis in human lung epithelial cells: triggering by paraquat and modulation by antioxidants[J]. Cell Biol Int, 1998, 22(9-10):671-678.

[18] Li X, Sun AY. Paraquat induced activation of transcription factor AP-1 and apoptosis in PC12 cells[J]. J Neural Transm, 1999, 106(1):1-21.

[19] Vincenzo Mollace, Michelangelo Iannone, Carolina Muscoli, et al. The role of oxidative stress in paraquat-induced neurotoxicity in rats: protection by non peptidyl superoxide dismutase mimetic[J]. Neurosci Lett, 2003, 335(3):163-166.

[20] Pol Gime′ nez-Xavier Pol, Roser Francisco, Antonio F Santidria′n, et al. Effects of dopamine on LC3-II activation as a marker of autophagy in a neuroblastoma cell model[J]. Neurotoxicology, 2009, 30(4):658-665.

[21] Shawna Tazik, Shakevia Johnson, Deyin Lu, et al. Comparative neuroprotective effects of rasagiline and aminoindan with selegiline on dexamethasone-induced brain cell apoptosis[J]. Neurotox Res, 2009, 15(3):284-290.

[22] Danuta Jantas , Wladyslaw Lason . Different mechanisms of NMDA-mediated protection against neuronal apoptosis: a stimuli-dependent effect[J]. Neurochem Res, 2009, 34(11):2040-2054.

[23] 金恵铭,王建枝.病理生理学[M].第六版. 北京: 人民卫生出版社, 2004: 130-134.

[24] James R. Roede , Jason M. Hansen , Young-Mi Go , et al. Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system[J]. Toxicol Sci, 2011, 121(2):368-375.

[25] Sanchez-Ramos JR, Hefti F, Weiner WJ. Paraquat and Parkinson's disease[J]. Neurology, 1987, 37(4):728.

[26] Naveen Kumar Singhal , Garima Srivastava , Devendra Kumar Patel ,et al. Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse[J]. J Pineal Res, 2011, 50(2):97-109.

[27] Sadie Costello, Myles Cockburn, Jeff Bronstein, et al. Parkinson’s Disease and Residential Exposure to Maneb and Paraquat From Agricultural Applications in the Central Valley of California[J]. J American Epidemiol, 2009, 169(9):919-926.

[28] Katarzyna Kuter, Maria ?mia?owska, Joanna Wierońska, et al. Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats[J]. Brain Res, 2007, 1155:196–207.

[29] Horng-huei Liou , Rong-chi Chen , Yuan-feen Tsai , et al. Effects of paraquat on the substantia nigra of the wistar rats: neurochemical, histological, and behavioral studies[J]. Toxicol Appl Pharmacol, 1996, 137(1):34-41.

[30] Min Jeong Kang , Suk Ju Gil , Hyun Chul Koh . Paraquat induces alternation of the dopamine catabolic pathways and glutathione levels in the substantia nigra of mice[J]. Toxicol Lett, 2009, 188(2):148-152.

[31] Alison L. McCormack , Jennifer G. Atienza , Louisa C. Johnston , et al. Role of oxidative stress in paraquat-induced dopaminergic cell degeneration[J]. J Neurochem, 2005, 93(4):1030-1037.

[32] A.I Brooks , C.A Chadwick , H.A Gelbard , et al. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss[J]. Brain Res, 1999, 823(1-2):1-10.

[33] Wonsuk Yang , Linan Chen , Yunmin Ding , et al. Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice[J]. Hum Mol Genet, 2007, 16(23):2900-2910.

[34] Pablo R Castello , Derek A Drechsel , Manisha Patel . Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain[J]. J Biol Chem, 2007, 282(19):14186-14193.

[35] R.J Dinis-Oliveira , F. Remião , H. Carmo , et al. Paraquat exposure as an etiological factor of Parkinson's disease[J]. Neurotoxicology, 2006, 27(6):1110-1122.

[36] Masato Enari , Hideki Sakahira , Hideki Yokoyama , et al. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [J]. Nature, 1998, 391(6662):43-50.

[37] Aimee L Edinger , Craig B Thompson . Death by design: apoptosis, necrosis and autophagy[J]. Curr Opin Cell Biol, 2004, 16(6):663-669.

[38] 胡野, 凌志强, 单小云, 等. 细胞凋亡的分子生物学[M]. 第一版. 北京: 军事医学科学出版社, 2002:511-515.

[39] Senthil Selvaraj , John A. Watt , Brji B Singh . TRPC1 inhibits apoptotic cell degeneration induced by dopaminergic neurotoxin MPTP/MPP(+)[J]. Cell Calcium, 2009,46(3):209-218.

[40] Green Douglas R, Kroemer Guido. The pathophysiology of mitochondrial cell death[J]. Science, 2004, 305(5684):626-629.

[41] Gary Fiskum , Anatoly Starkov , Brain M. Polster , et al. Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson's disease[J]. Ann N Y Acad Sci, 2003, 991:111-119.

[42] Fei Qingyan, Alison L. McCormack, Donato A. Di Monte, et al. Paraquat neurotoxicity is mediated by a Bak-dependent mechanism[J]. J Biol Chem, 2008, 283(6):3357-3364.

[43] Miquel Vila , David Ramonet , Celine Perier . Mitochondrial alterations in Parkinson’s disease: new clues[J]. J Neurochem, 2008, 107(2):317-328.

[44] Oren A Levy , Cristina Malagelada , LloydA Greene .Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps[J]. Apoptosis, 2009, 14(4):478-500.

[45] Mireia Niso-Santano , Jose M. Morán , Lourdes García-Rubio , et al. Low concentrations of paraquat induces early activation of extracellular signal-regulated kinase 1/2, protein kinase B, and c-Jun N-terminal kinase 1/2 pathways: role of c-Jun N-terminal kinase in paraquat-induced cell death[J]. Toxicol Sci, 2006, 92(2):507-515.

[46] Sarah J Harper , Philip LoGrasso . Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38[J]. Cell Signal, 2001, 13(5):299-310.

[47] Cha Guang-Ho, Kim Sunhong, Park Jeehye, et al. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila[J]. Proc Natl Acad Sci USA, 2005, 102(29):10345-10350.

[48] Anna C. Maroney , James P. Finn , Thomas J. Connors , et al. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family[J]. J Biol Chem, 2001, 276(27):25302-25308.

[49] Michael S. Saporito, Ellen M Brown, Matthew S. Miller, et al. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4- phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo[J]. J Pharmacol Exp Ther, 1999, 288(2):421–427.

[50] Xia Xu-Gang, Harding Thomas, Weller Michael, et al. Gene transfer of the JNK interacting protein- 1 protects dopaminergic neurons in the MPTP model of Parkinson’s disease[J]. Proc Natl Acad Sci USA, 2001, 98(18): 10433–10438.

[51] González-Polo Rosa A, Soler German, Alvarez Alberto, et al. Vitamin E blocks early events induced by 1-methyl-4-phenylpyridinium (MPP+) in cerebellar granule cells[J]. J Neurochem, 2003, 84(2):305-315.

[52] Jose M Moran , Rosa A. Gonzalez-Polo , Miguel A. Ortiz-Ortiz , et al. Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways[J]. J Toxicol Environ Health A, 2008, 71(22):1457-1467.

[53] Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? [J]. Lancet Neurol, 2009, 8(4): 382–397.

[54] Miquel Vila , Vernice Jackson-Lewis , Slobodanka Vukosavic , et al. Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease[J]. Proc Natl Acad Sci U S A, 2001, 98(5):2837-2842.

[55] Javier Simón-Sánchez , Claudia Schulte , Jose M. Bras , et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease[J]. Nat Genet, 2009, 41(12):1308-1312.

[56] 鞠躬, 吕国蔚, 王百忍, 等. 神经生物学[M]. 第一版. 北京: 人民卫生出版社, 2004:654-659.

[57] Simunovic Filip, Yi Ming, Wang Yulei, et al. Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology[J]. Brain, 2009, 132(Pt 7):1795-1809.

[58] Gollamudi Seema, Johri Ashu, Calingasan Noel Y, et al. Concordant signaling pathways produced by pesticide exposure in mice correspond to pathways identified in human Parkinson's disease[J]. PLoS One, 2012,7(5):e36191.