Document Detail

Vacuolar H+ -ATPase c protects glial cell death induced by sodium nitroprusside under glutathione-depleted condition.
MedLine Citation:
PMID:  21433058     Owner:  NLM     Status:  MEDLINE    
We examined the role of the c subunit (ATP6L) of vacuolar H(+) -ATPase and its molecular mechanisms in glial cell death induced by sodium nitroprusside (SNP). ATP6L siRNA-transfected cells treated with SNP showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, but reduction of ATP6L did not affect the regulation of lysosomal pH in analyses with lysosomal pH-dependent fluorescence probes. Photodegraded SNP and ferrous sulfate induced cytotoxicity with the same pattern as that of SNP, but SNAP and potassium cyanide did not show activity. Pretreatment of the transfected cells with deferoxamine (DFO) reduced ROS production and significantly inhibited the cytotoxicity, which indicates that primarily iron rather than nitric oxide or cyanide from SNP contributes to cell death. Involvement of apoptotic processes in the cells was not shown. Pretreatment with JNK or p38 chemical inhibitor significantly inhibited the cytotoxicity, and we also confirmed that the MAPKs were activated in the cells by immunoblot analysis. Significant increase of LC3-II conversion was observed in the cells, and the conversions were inhibited by cotransfection of the MAPK siRNAs and pretreatment with DFO. Introduction of Atg5 siRNA inhibited the cytotoxicity and inhibited the activation of MAPKs and the conversion of LC3. We finally confirmed autophagic cell death and involvement of MAPKs by observation of autophagic vacuoles via electron microscopy. These data suggest that ATP6L has a protective role against SNP-induced autophagic cell death via inhibition of JNK and p38 in GSH-depleted glial cells.
Yu Jeong Byun; Seong-Beom Lee; Hwa Ok Lee; Min Jeong Son; Ho-Shik Kim; Oh-Joo Kwon; Seong-Whan Jeong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  112     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-13     Completed Date:  2011-11-02     Revised Date:  2011-11-04    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1985-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
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MeSH Terms
Autophagy / drug effects*,  genetics
Buthionine Sulfoximine / pharmacology
Cell Line, Tumor
Enzyme Activation / drug effects,  genetics
Hydrogen-Ion Concentration
Lysosomes / enzymology,  ultrastructure
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors,  genetics,  metabolism
Neuroglia / enzymology*,  ultrastructure
Nitric Oxide Donors / pharmacology*
Nitroprusside / pharmacology*
Oxidation-Reduction / drug effects
Protein Kinase Inhibitors / pharmacology
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors,  genetics,  metabolism*
Reg. No./Substance:
0/Nitric Oxide Donors; 0/Protein Kinase Inhibitors; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 15078-28-1/Nitroprusside; 5072-26-4/Buthionine Sulfoximine; 70-18-8/Glutathione; EC Protein Kinase Kinases; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases; EC protein, human

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

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