Proteasome Inhibitor Does Not Enhance MPTP Neurotoxicity in Mice
| Autor: | Masahiro Umeda, Naoto Kadoguchi, Hiroyuki Kato, Tsutomu Araki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Proteasome Endopeptidase Complex Tyrosine 3-Monooxygenase Dopamine Neurotoxins Substantia nigra Cysteine Proteinase Inhibitors Biology Pharmacology Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Parkinsonian Disorders Glial Fibrillary Acidic Protein medicine Animals Neurons Tyrosine hydroxylase Glial fibrillary acidic protein MPTP Dopaminergic Neurotoxicity Drug Synergism Cell Biology General Medicine medicine.disease Molecular biology nervous system diseases Mice Inbred C57BL Substantia Nigra Disease Models Animal nervous system chemistry Proteasome 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Proteasome inhibitor biology.protein Oligopeptides medicine.drug |
| Zdroj: | Cellular and Molecular Neurobiology. 28:971-979 |
| ISSN: | 1573-6830 0272-4340 |
| Popis: | Dysfunction of the proteasome function is known to be a potential mechanism for dopaminergic neuron degeneration. Here, we investigated to determine whether systematic administration of proteasome inhibitor, carbobenzoxy-L-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI), causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. PSI was injected into MPTP-treated mice over a period of 2 weeks. Thereafter, we evaluated the effect of PSI 2, 4, and 8 weeks after the cessation of treatment with PSI. In the present study with HPLC analysis, PSI did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Our present study with Western blot analysis also demonstrated that the reduction of tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) protein levels in MPTP-treated mice was more pronounced than that in MPTP + PSI-treated animals. These results suggest that proteasome inhibitor did not enhance MPTP neurotoxicity in mice. Our findings suggest that proteasome inhibition is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of Parkinson's disease. |
| Databáze: | OpenAIRE |
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