Document Detail


Inhibition of MG132-induced mitochondrial dysfunction and cell death in PC12 cells by 3-morpholinosydnonimine.
MedLine Citation:
PMID:  15725397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of 3-morpholinosydnonimine (SIN-1) against the cytotoxicity of MG132, a proteasome inhibitor, in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with MG132 resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS), and depletion of GSH. Addition of SIN-1, a producer of nitric oxide (NO) and superoxide, differentially reduced the MG132-induced cell death and GSH depletion concentration dependently with a maximal inhibitory effect at 150 microM. Carboxy-PTIO, superoxide dismutase, Mn-TBAP, and ascorbate prevented the inhibitory effect of SIN-1 on the cytotoxicity of MG132. SIN-1 inhibited the MG132-induced change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents in PC12 cells. S-nitroso-N-acetyl-DL-penicillamine reduced the MG132-induced cell death in PC12 cells, whereas peroxynitrite and H2O2 did not affect the cytotoxicity of MG132. The results suggest that NO and superoxide liberated from SIN-1 exert an inhibitory effect against the cytotoxicity of MG132. SIN-1 may inhibit the MG132-induced viability loss in PC12 cells by suppressing change in the mitochondrial membrane permeability that is associated with oxidative damage.
Authors:
Chung Soo Lee; Eun Sook Han; Eon Sob Park; Hyoweon Bang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain research     Volume:  1036     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-23     Completed Date:  2005-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  18-26     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Cell Death / drug effects,  physiology
Cell Membrane Permeability / drug effects,  physiology
Cysteine Proteinase Inhibitors / toxicity
Cytochromes c / metabolism
Dose-Response Relationship, Drug
Energy Metabolism / drug effects,  physiology*
Enzyme Inhibitors / pharmacology
Free Radicals / metabolism
Glutathione / metabolism
Leupeptins / antagonists & inhibitors*,  toxicity
Mitochondria / drug effects,  metabolism*
Molsidomine / analogs & derivatives*,  pharmacology*
Nitric Oxide / antagonists & inhibitors*,  metabolism
Nitric Oxide Donors / pharmacology
Oxidative Stress / drug effects,  physiology*
PC12 Cells
Proteasome Endopeptidase Complex / antagonists & inhibitors,  metabolism
Rats
Superoxides / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cysteine Proteinase Inhibitors; 0/Enzyme Inhibitors; 0/Free Radicals; 0/Leupeptins; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 70-18-8/Glutathione; 9007-43-6/Cytochromes c; EC 3.4.25.1/Proteasome Endopeptidase Complex

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


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