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Neurotoxicity Research

Erschienen in:

01.11.2015 | Original Article

Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson’s Disease

verfasst von: Chandrashekhar Voshavar, Mrudang Shah, Liping Xu, Aloke K. Dutta

Erschienen in: Neurotoxicity Research | Ausgabe 4/2015

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Abstract

Oxidative stress has been strongly implicated in the progression of Parkinson’s disease (PD). Depletion of cytoplasmic glutathione levels is one of the indications of oxidative stress, which occur in the substantia nigra of PD patients at an early stage of the disease process. It has been shown that glutathione depletion causes the inhibition of mitochondrial complex I, thus affecting mitochondrial function leading to oxidative stress via production of reactive oxygen species. Studies were carried out to investigate the role of D-512, a potent multifunctional neuroprotective D2/D3 receptor agonist, in protecting dopaminergic PC12 cells treated with buthionine sulfoximine (BSO), an inhibitor of key enzyme in glutathione synthesis and 6-hydroxydopamine (6-OHDA), a widely used neurotoxin. D-512 was able to restore level of glutathione against BSO/6-OHDA-mediated glutathione depletion. D-512 also showed significant neuroprotection in PC12 cells against toxicity induced by combined treatment of BSO and 6-OHDA. Furthermore, D-512 was able to restore both phospho-extracellular signal-regulated kinase and phospho-Jun N-terminal kinase levels upon treatment with 6-OHDA providing an evidence on the possible mechanism of action for neuroprotection by modulating mitogen-activated protein kinases. We have further demonstrated the neuroprotective effects of D-512 against oxidative insult produced by BSO and 6-OHDA in PC12 cells.

Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997a) A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69:1326–1329CrossRefPubMed

Alam ZI et al (1997b) Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem 69:1196–1203CrossRefPubMed

Bergman H, Deuschl G (2002) Pathophysiology of Parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov Disord 17(Suppl 3):S28–S40 official journal of the Movement Disorder Society CrossRefPubMed

Blum D, Torch S, Nissou MF, Benabid AL, Verna JM (2000) Extracellular toxicity of 6-hydroxydopamine on PC12 cells. Neurosci Lett 283:193–196CrossRefPubMed

Choi WS, Yoon SY, Oh TH, Choi EJ, O’Malley KL, Oh YJ (1999) Two distinct mechanisms are involved in 6-hydroxydopamine- and MPP+-induced dopaminergic neuronal cell death: role of caspases, ROS, and JNK. J Neurosci Res 57:86–94CrossRefPubMed

Davila D, Torres-Aleman I (2008) Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell 19:2014–2025. doi:10.1091/mbc.E07-08-0811 CrossRefPubMedPubMedCentral

de Pablos RM, Herrera AJ, Espinosa-Oliva AM, Sarmiento M, Munoz MF, Machado A, Venero JL (2014) Chronic stress enhances microglia activation and exacerbates death of nigral dopaminergic neurons under conditions of inflammation. J Neuroinflammation 11:34. doi:10.1186/1742-2094-11-34 CrossRefPubMedPubMedCentral

Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567. doi:10.1038/sj.onc.1207107 CrossRefPubMed

Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074. doi:10.1155/2010/214074 PubMedPubMedCentral

Garcia JC, Remires D, Leiva A, Gonzalez R (2000) Depletion of brain glutathione potentiates the effect of 6-hydroxydopamine in a rat model of Parkinson’s disease. J Mol Neurosci 14:147–153. doi:10.1385/JMN:14:3:147 CrossRefPubMed

Gille G, Reichmann H (2011) Iron-dependent functions of mitochondria–relation to neurodegeneration. J Neural Transm 118:349–359. doi:10.1007/s00702-010-0503-7 CrossRefPubMed

Griffith OW (1982) Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis. J Biol Chem 257:13704–13712PubMed

Hwang O (2013) Role of oxidative stress in Parkinson’s disease. Exp Neurobiol 22:11–17. doi:10.5607/en.2013.22.1.11 CrossRefPubMedPubMedCentral

Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36CrossRefPubMed

Jenner P, Dexter DT, Sian J, Schapira AH, Marsden CD, The Royal Kings and Queens Parkinson’s Disease Research Group (1992) Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease. Ann Neurol 32(Suppl):S82–S87CrossRefPubMed

Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47:S161–S170CrossRefPubMed

Johnson M, Antonio T, Reith ME, Dutta AK (2012) Structure-activity relationship study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydroben zo[d]thiazole-2,6-diamine analogues: development of highly selective D3 dopamine receptor agonists along with a highly potent D2/D3 agonist and their pharmacological characterization. J Med Chem 55:5826–5840. doi:10.1021/jm300268s CrossRefPubMedPubMedCentral

Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345:91–104. doi:10.1007/s11010-010-0563-x CrossRefPubMed

Keshet Y, Seger R (2010) The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 661:3–38. doi:10.1007/978-1-60761-795-2_1 CrossRefPubMed

Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Investig 111:785–793. doi:10.1172/JCI18182 CrossRefPubMedPubMedCentral

Li H, Wu S, Chen J, Wang B, Shi N (2013) Effect of glutathione depletion on Nrf2/ARE activation by deltamethrin in PC12 Cells. Arhiv za higijenu rada i toksikologiju 64:87–97. doi:10.2478/10004-1254-64-2013-2251 CrossRefPubMed

Linert W, Jameson GN (2000) Redox reactions of neurotransmitters possibly involved in the progression of Parkinson’s disease. J Inorg Biochem 79:319–326CrossRefPubMed

Martin HL, Teismann P (2009) Glutathione–a review on its role and significance in Parkinson’s disease. FASEB J 23:3263–3272. doi:10.1096/fj.08-125443 official publication of the Federation of American Societies for Experimental Biology CrossRefPubMed

McCubrey JA, Lahair MM, Franklin RA (2006) Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal 8:1775–1789. doi:10.1089/ars.2006.8.1775 CrossRefPubMed

Mnich K, Finn DP, Dowd E, Gorman AM (2010) Inhibition by anandamide of 6-hydroxydopamine-induced cell death in PC12 cells. Int J Cell Biol 2010:818497. doi:10.1155/2010/818497 CrossRefPubMedPubMedCentral

Morrison RS, Kinoshita Y, Johnson MD, Ghatan S, Ho JT, Garden G (2002) Neuronal survival and cell death signaling pathways. Adv Exp Med Biol 513:41–86CrossRefPubMed

Ochu EE, Rothwell NJ, Waters CM (1998) Caspases mediate 6-hydroxydopamine-induced apoptosis but not necrosis in PC12 cells. J Neurochem 70:2637–2640CrossRefPubMed

Park HJ, Park KH, Shin KS, Lee MK (2013) The roles of cyclic AMP-ERK-Bad signaling pathways on 6-hydroxydopamine-induced cell survival and death in PC12 cells. Toxicol In Vitro 27:2233–2241. doi:10.1016/j.tiv.2013.09.014 an international journal published in association with BIBRA CrossRefPubMed

Perry TL, Godin DV, Hansen S (1982) Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 33:305–310CrossRefPubMed

Reiter RJ (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533 official publication of the Federation of American Societies for Experimental Biology PubMed

Santra S, Xu L, Shah M, Johnson M, Dutta A (2013) D-512 and D-440 as novel multifunctional dopamine agonists: characterization of neuroprotection properties and evaluation of in vivo efficacy in a Parkinson’s disease animal model. ACS Chem Neurosci. doi:10.1021/cn400106n PubMedPubMedCentral

Seaton TA, Jenner P, Marsden CD (1996) Thioctic acid does not restore glutathione levels or protect against the potentiation of 6-hydroxydopamine toxicity induced by glutathione depletion in rat brain. J Neural Transm 103:315–329CrossRefPubMed

Selley ML (1998) (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med 25:169–174CrossRefPubMed

Seth K, Agrawal AK, Aziz MH, Ahmad A, Shukla Y, Mathur N, Seth PK (2002) Induced expression of early response genes/oxidative injury in rat pheochromocytoma (PC12) cell line by 6-hydroxydopamine: implication for Parkinson’s disease. Neurosci Lett 330:89–93CrossRefPubMed

Shafer TJ, Atchison WD (1991) Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxicological studies. Neurotoxicology 12:473–492PubMed

Shah M et al (2014) The high-affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of Parkinson’s disease. J Neurochem 131:74–85. doi:10.1111/jnc.12767 CrossRefPubMed

Shen XM, Dryhurst G (1996) Further insights into the influence of l-cysteine on the oxidation chemistry of dopamine: reaction pathways of potential relevance to Parkinson’s disease. Chem Res Toxicol 9:751–763. doi:10.1021/tx960008f CrossRefPubMed

Shimizu E, Hashimoto K, Komatsu N, Iyo M (2002) Roles of endogenous glutathione levels on 6-hydroxydopamine-induced apoptotic neuronal cell death in human neuroblastoma SK-N-SH cells. Neuropharmacology 43:434–443CrossRefPubMed

Sian J et al (1994a) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355. doi:10.1002/ana.410360305 CrossRefPubMed

Sian J, Dexter DT, Lees AJ, Daniel S, Jenner P, Marsden CD (1994b) Glutathione-related enzymes in brain in Parkinson’s disease. Ann Neurol 36:356–361. doi:10.1002/ana.410360306 CrossRefPubMed

Sofic E, Lange KW, Jellinger K, Riederer P (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 142:128–130CrossRefPubMed

Spencer JP, Jenner P, Daniel SE, Lees AJ, Marsden DC, Halliwell B (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: possible mechanisms of formation involving reactive oxygen species. J Neurochem 71:2112–2122CrossRefPubMed

Takata MK et al (2005) Neuroprotective effect of D-psicose on 6-hydroxydopamine-induced apoptosis in rat pheochromocytoma (PC12) cells. J Biosci Bioeng 100:511–516. doi:10.1263/jbb.100.511 CrossRefPubMed

Westerink RH, Ewing AG (2008) The PC12 cell as model for neurosecretion. Acta Physiol 192:273–285. doi:10.1111/j.1748-1716.2007.01805.x CrossRef

Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5:863–873. doi:10.1038/nrn1537 CrossRefPubMed

Zhang LJ et al (2012) Human albumin prevents 6-hydroxydopamine-induced loss of tyrosine hydroxylase in in vitro and in vivo. PLoS One 7:e41226. doi:10.1371/journal.pone.0041226 CrossRefPubMedPubMedCentral

Zhang W, Liu HT (2002) MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 12:9–18. doi:10.1038/sj.cr.7290105 CrossRefPubMed

Zhou C, Huang Y, Przedborski S (2008) Oxidative stress in Parkinson’s disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 1147:93–104. doi:10.1196/annals.1427.023 CrossRefPubMedPubMedCentral

Titel: Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson’s Disease
verfasst von: Chandrashekhar Voshavar
Mrudang Shah
Liping Xu
Aloke K. Dutta
Publikationsdatum: 01.11.2015
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 4/2015
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-015-9548-6

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