Linked Life Data

16125053

Source:http://linkedlifedata.com/resource/pubmed/id/16125053

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-8-29
pubmed:abstractText
Wasting of skeletal muscle (cachexia) is associated with a variety of chronic or inflammatory disorders and has long been recognized as a poor prognostic sign. It is currently accepted that the cytokine tumor necrosis factor alpha (TNF-alpha; cachectin) plays a key role in the development of this condition. TNF-alpha-induced apoptotic cell death represents a potential mechanism by which muscle wasting can occur. Evidence has accumulated that the cytokine interferon gamma (IFN-gamma) may act as a modulator of TNF-alpha signalling. Thus, the present study was designed to elucidate if TNF-alpha can directly induce apoptosis in differentiated myotubes, to assess the potential anti-apoptotic properties of IFN-gamma and to get insight into the signalling pathways implicated in the modulatory effects of IFN-gamma. Myoblasts of the murine cell line C2C12 were allowed to differentiate in a low serum containing media and myogenesis assessed by muscle specific protein expression. Non-proliferating, polynucleated, fully differentiated myotubes were obtained after seven days in differentiation media. Exposure of C2C12 myotubes to TNF-alpha for 48 h induced apoptosis characterized by enhanced caspase-3 activity, which resulted in poly(ADP-ribose) polymerase (PARP) cleavage and increased histone-associated-DNA fragmentation. These effects were fully reverted in the presence of IFN-gamma. This cytokine induced down-regulation of the subtype 2 of TNF-alpha receptors (TNF-R2), enhanced TNF-alpha-induced NF-kappaB translocation to the nucleus and binding to DNA and increased the immunoreactivity of the protein c-IAP1, a member of the inhibitor of apoptosis (IAP) gene family whose synthesis is stimulated by NF-kappaB at the transcriptional level. Together, these results demonstrate that TNF-alpha directly induces apoptosis in differentiated myotubes and suggest that the cytokine IFN-gamma, might represent a new immunoadjuvant therapeutic tool for managing cachexia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1333-42
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16125053-Active Transport, Cell Nucleus, pubmed-meshheading:16125053-Animals, pubmed-meshheading:16125053-Apoptosis, pubmed-meshheading:16125053-Caspase 3, pubmed-meshheading:16125053-Caspases, pubmed-meshheading:16125053-Cell Differentiation, pubmed-meshheading:16125053-Cell Line, pubmed-meshheading:16125053-Down-Regulation, pubmed-meshheading:16125053-Inhibitor of Apoptosis Proteins, pubmed-meshheading:16125053-Interferon-gamma, pubmed-meshheading:16125053-Mice, pubmed-meshheading:16125053-Muscle Development, pubmed-meshheading:16125053-Muscle Fibers, Skeletal, pubmed-meshheading:16125053-Myoblasts, pubmed-meshheading:16125053-NF-kappa B, pubmed-meshheading:16125053-Poly(ADP-ribose) Polymerases, pubmed-meshheading:16125053-Receptors, Tumor Necrosis Factor, Type II, pubmed-meshheading:16125053-Recombinant Proteins, pubmed-meshheading:16125053-Signal Transduction, pubmed-meshheading:16125053-Tumor Necrosis Factor-alpha
pubmed:year
2005
pubmed:articleTitle
IFN-gamma prevents TNF-alpha-induced apoptosis in C2C12 myotubes through down-regulation of TNF-R2 and increased NF-kappaB activity.
pubmed:affiliation
Institut Universitari d'Investigacions en Ciències de la Salut/Departament de Biologia, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't