| Inhibition of MG132-induced mitochondrial dysfunction and cell death in PC12 cells by 3-morpholinosydnonimine. | |
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MedLine Citation:
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PMID: 15725397 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Chung Soo Lee; Eun Sook Han; Eon Sob Park; Hyoweon Bang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Brain research Volume: 1036 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-02-23 Completed Date: 2005-06-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 18-26 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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