Abstract
Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased stabilization of p53 upregulated the level of Bax and mitochondrial depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132-induced cell death. These results suggest that p53 is a candidate as an intermediary between the proteasome system and mitochondria-related neuronal death in PD.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Benzimidazoles / metabolism
-
Benzothiazoles
-
Blotting, Western / methods
-
Carbocyanines / metabolism
-
Cell Death / drug effects
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
Cysteine Endopeptidases
-
Cysteine Proteinase Inhibitors / pharmacology
-
Dopamine / metabolism*
-
Dose-Response Relationship, Drug
-
Drug Interactions
-
Fluorescent Antibody Technique / methods
-
Humans
-
Leupeptins / pharmacology*
-
Membrane Potentials / drug effects
-
Mitochondria / drug effects*
-
Mitochondria / metabolism
-
Multienzyme Complexes / antagonists & inhibitors*
-
Neuroblastoma
-
Proteasome Endopeptidase Complex
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-bcl-2*
-
Thiazoles / pharmacology
-
Time Factors
-
Toluene / analogs & derivatives*
-
Toluene / pharmacology
-
Tumor Suppressor Protein p53 / metabolism*
-
bcl-2-Associated X Protein
Substances
-
BAX protein, human
-
Benzimidazoles
-
Benzothiazoles
-
Carbocyanines
-
Cysteine Proteinase Inhibitors
-
Leupeptins
-
Multienzyme Complexes
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Thiazoles
-
Tumor Suppressor Protein p53
-
bcl-2-Associated X Protein
-
5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine
-
Toluene
-
pifithrin
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex
-
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
-
Dopamine