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: Anubhuti Dixit, Garima Srivastava, Divya Verma, Manisha Mishra, Pradhyumna Kumar Singh, Om Prakash, Mahendra Pratap Singh
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1832 Issue 8 Pg. 1227-40 (Aug 2013) ISSN: 0006-3002 [Print] Netherlands
• PMID: 23562983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antiparkinson Agents
• Homeodomain Proteins
• Metalloporphyrins
• Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
• Proteome
• Shox2 protein, mouse
• Stathmin
• Maneb
• Levodopa
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Superoxide Dismutase
• Minocycline
• Paraquat
• Dopamine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Antiparkinson Agents (pharmacology)
• Disease Models, Animal
• Dopamine (metabolism)
• Homeodomain Proteins (metabolism)
• Levodopa (pharmacology)
• Male
• Maneb
• Metalloporphyrins (pharmacology)
• Mice
• Microglia (metabolism)
• Minocycline (pharmacology)
• Mitochondria (drug effects, metabolism)
• Paraquat
• Parkinson Disease, Secondary (etiology, metabolism)
• Proteome (metabolism)
• Stathmin (metabolism)
• Superoxide Dismutase (metabolism)