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TNF-alpha-mediated apoptosis in chondrocytes sensitized by MG132 or actinomycin D

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Authors
Kim, Hyun A.; Song, Yeong W.
Issue Date
2002
Publisher
Elsevier
Citation
Biochem. Biophys. Res. Commun. 295 (2005) 937-944
Keywords
Annexin A5/pharmacology*ApoptosisBlotting, WesternCaspases/antagonists & inhibitorsCell Nucleus/metabolismChondrocytes/*metabolism/pathologyCysteine Proteinase Inhibitors/pharmacologyDactinomycin/metabolism/*pharmacologyFlow CytometryI-kappa B Proteins/metabolismLeupeptins/*pharmacologyNF-kappa B/metabolismProtein Synthesis Inhibitors/pharmacologyRecombinant Proteins/metabolismSignal TransductionTime FactorsTumor Necrosis Factor-alpha/*metabolismTumor Suppressor Protein p53/metabolism
Abstract
The mechanism of TNF-alpha-mediated chondrocyte apoptosis in human articular cartilage was investigated. First passage OA chondrocytes were treated with actinomycin D or MG132 in combination with TNF-alpha to facilitate cell death. The patterns of apoptosis-related proteins, NF-kappaB activation, and IkappaB degradation were analyzed. Cell death was increased by 0.2 microg/ml of actinomycin D or 20 microM MG132 in combination with TNF-alpha. Apoptosis potentiated by MG132 was more effectively inhibited by caspase inhibitors than that by actinomycin D. MG132 or actinomycin D both led to a significant increase in p53, but the expressions of the p53 response proteins increased only in MG132 treated chondrocytes. TNF-alpha induced chondrocyte IkappaB phosphorylation was unaffected by either MG132 or actinomycin D. MG132, but not actinomycin D, inhibited the chondrocyte IkappaB degradation induced by TNF-alpha and NF-kappaB activation. Our results suggest that MG132 and actinomycin D exert different influences upon TNF-alpha-mediated chondrocyte apoptotic signaling.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12127985

http://hdl.handle.net/10371/12128
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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