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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-2-25
pubmed:abstractText
Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. NO-induced oxidative stress has been proposed in the pathogenesis of muscle tissue damage in inclusion-body myositis (IBM), which is characterized by deposition of beta-amyloid protein (Abeta) in vacuolated muscle fibres. To determine whether Abeta can induce NO production in skeletal muscle, we stimulated C2C12 mouse skeletal muscle cells in vitro with Abeta[1-42] or Abeta[25-35] peptides in the presence or absence of interferon gamma (IFN-gamma). Neither Abeta peptides nor IFN-gamma were able to stimulate nitrite (NO(2)(-)) production by C2C12 cells when given alone. However, combination of IFN-gamma with either Abeta[1-42] or Abeta[25-35] resulted in significant NO(2)(-) release into cell-free supernatants. Northern blot analysis of RNA obtained from Abeta/IFN-gamma-stimulated C2C12 cells revealed increased mRNA accumulation of inducible nitric oxide synthase (iNOS). Moreover, approximately 4% of muscle cells incubated with Abeta peptides and IFN-gamma showed ultrastructural features of DNA fragmentation. These findings, taken together, indicate that the association of Abeta with IFN-gamma stimulates NO(2)(-) production via induction of iNOS gene expression in skeletal muscle cells, with occasional evidence for nuclear changes suggesting apoptotic morphology. These data further support a role for Abeta deposition in the pathogenesis of postulated oxidative damage in IBM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
123 ( Pt 2)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
374-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells.
pubmed:affiliation
Institute of Neurology, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't