Synergistic effect of β-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells

Pierluigi Baron, Daniela Galimberti, Lucia Meda, Elisabetta Prat, Elio Scarpini, Giancarlo Conti, Maurizio Moggio, Alessandro Prelle, Guglielmo Scarlato

Research output: Contribution to journalArticle

Abstract

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 β-amyloid protein (Aβ) in vacuolated muscle fibres. To determine whether Aβ can induce NO production in skeletal muscle, we stimulated C2C12 mouse skeletal muscle cells in vitro with Aβ[1-42] or Aβ[25-35] peptides in the presence or absence of interferon gamma (IFN-γ). Neither Aβ peptides nor IFN-γ were able to stimulate nitrite (NO2 -) production by C2C12 cells when given alone. However, combination of IFN-γ with either Aβ[1-42] or Aβ[25-35] resulted in significant NO2 - release into cell-free supernatants. Northern blot analysis of RNA obtained from Aβ/IFN-γ-stimulated C2C12 cells revealed increased mRNA accumulation of inducible nitric oxide synthase (iNOS). Moreover, ~4% of muscle cells incubated with Aβ peptides and IFN-γ showed ultrastructural features of DNA fragmentation. These findings, taken together, indicate that the association of Aβ with IFN-γ stimulates NO2 - 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 Aβ deposition in the pathogenesis of postulated oxidative damage in IBM.

Original languageEnglish
Pages (from-to)374-379
Number of pages6
JournalBrain
Volume123
Issue number2
Publication statusPublished - Feb 2000

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Keywords

  • β-amyloid
  • Apoptosis
  • IBM
  • Muscle cell
  • Nitric oxide

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Baron, P., Galimberti, D., Meda, L., Prat, E., Scarpini, E., Conti, G., Moggio, M., Prelle, A., & Scarlato, G. (2000). Synergistic effect of β-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells. Brain, 123(2), 374-379.