Document Detail

N-methylated beta-carbolines protect PC12 cells from cytotoxic effect of MPP+ by attenuation of mitochondrial membrane permeability change.
MedLine Citation:
PMID:  12804796     Owner:  NLM     Status:  MEDLINE    
Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of beta-carbolines (harmaline and harmalol) on the MPP(+)-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. beta-Carbolines and antioxidants (superoxide dismutase, catalase, ascorbate or rutin) prevented the loss of cell viability in PC12 cells treated with 250 microM MPP(+), while the effects of N-acetylcysteine and dithiothreitol were not observed. beta-Carbolines reduced the condensation and fragmentation of nuclei caused by MPP(+) in PC12 cells. beta-Carbolines alone did not exhibit a significant cytotoxic effect on PC12 cells. beta-Carbolines (50 microM) inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, activation of caspase-3, formation of reactive oxygen species (ROS) and depletion of GSH caused by MPP(+) in PC12 cells. beta-Carbolines reduced the hydrogen peroxide- or SIN-1-induced cell death in PC12 cells. The results suggest that beta-carbolines may attenuate the MPP(+)-induced viability loss in PC12 cells by inhibition of change in the mitochondrial membrane permeability and by antioxidant effect.
Tai Hwan Park; Oh Sang Kwon; Se Young Park; Eun Sook Han; Chung Soo Lee
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Neuroscience research     Volume:  46     ISSN:  0168-0102     ISO Abbreviation:  Neurosci. Res.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-13     Completed Date:  2003-08-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8500749     Medline TA:  Neurosci Res     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  349-58     Citation Subset:  IM    
Department of Neurology, College of Medicine, Chung-Ang University, 156-756, Seoul, South Korea.
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MeSH Terms
1-Methyl-4-phenylpyridinium / pharmacology*
Analysis of Variance
Antioxidants / pharmacology
Apoptosis / drug effects
Carbolines / pharmacology*
Caspase 3
Caspases / metabolism
Cell Survival
Cytochrome c Group / metabolism
Dose-Response Relationship, Drug
Drug Interactions
Flow Cytometry
Glutathione / metabolism
Intracellular Membranes / drug effects*,  physiology
Mitochondria / drug effects*,  physiology
PC12 Cells
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Antioxidants; 0/Carbolines; 0/Cytochrome c Group; 0/Reactive Oxygen Species; 48134-75-4/1-Methyl-4-phenylpyridinium; 70-18-8/Glutathione; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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