title: Minocycline, levodopa and MnTMPyP induced changes in the mitochondrial proteome profile of MPTP and maneb and paraquat mice models of Parkinson's disease.
abstract: Mitochondrial dysfunction is the foremost perpetrator of the nigrostriatal dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, the roles played by majority of the mitochondrial proteins in PD pathogenesis have not yet been deciphered. The present study investigated the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and combined maneb and paraquat on the mitochondrial proteome of the nigrostriatal tissues in the presence or absence of minocycline, levodopa and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP). The differentially expressed proteins were identified and proteome profiles were correlated with the pathological and biochemical anomalies induced by MPTP and maneb and paraquat. MPTP altered the expression of twelve while combined maneb and paraquat altered the expression of fourteen proteins. Minocycline, levodopa and MnTMPyP, respectively, restored the expression of three, seven and eight proteins in MPTP and seven, eight and eight proteins in maneb- and paraquat-treated groups. Although levodopa and MnTMPyP rescued from MPTP- and maneb- and paraquat-mediated increase in the microglial activation and decrease in manganese-superoxide dismutase expression and complex I activity, dopamine content and number of dopaminergic neurons, minocycline defended mainly against maneb- and paraquat-mediated alterations. The results demonstrate that MPTP and combined maneb and paraquat induce mitochondrial dysfunction and microglial activation and alter the expression of a bunch of mitochondrial proteins leading to the nigrostriatal dopaminergic neurodegeneration and minocycline, levodopa or MnTMPyP variably offset scores of such changes.
authors.affiliation: CSIR-Indian Institute of Toxicology Research CSIR-IITR, M. G. Marg, Post Box-80, Lucknow-226 001, UP, India.
authors.forename: Anubhuti
authors.initials: A
authors.lastname: Dixit
authors.forename: Garima
authors.initials: G
authors.lastname: Srivastava
authors.forename: Divya
authors.initials: D
authors.lastname: Verma
authors.forename: Manisha
authors.initials: M
authors.lastname: Mishra
authors.forename: Pradhyumna Kumar
authors.initials: PK
authors.lastname: Singh
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008344:Maneb; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010269:Paraquat; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D050777:Stathmin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D018398:Homeodomain Proteins; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D020543:Proteome; C484663:Shox2 protein, mouse; D050777:Stathmin; D008344:Maneb; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013482:Superoxide Dismutase; D008911:Minocycline; D010269:Paraquat; D004298:Dopamine