Regulation of inducible nitric oxide synthase expression in L6 rat skeletal muscle cells

Am J Physiol. 1997 Jan;272(1 Pt 1):C35-40. doi: 10.1152/ajpcell.1997.272.1.C35.

Abstract

Cytokine-stimulated expression of inducible type of nitric oxide synthase (iNOS) seems to be regulated by various signal pathways in a cell-specific manner. In this study, we examined how it was regulated in L6 rat skeletal muscle cells. In L6 cells, the combination of interleukin-1 beta and interferon-gamma induced a marked accumulation of nitrite, a stable metabolite of nitric oxide. In parallel with this reaction, iNOS mRNA expression was achieved at a maximum between 3 and 6 h, and iNOS protein was detectable at 6 h and peaked at 24 h after stimulation. Tyrosine kinase inhibitors, herbimycin A, and genistein suppressed cytokine-induced iNOS expression and nitrite production. Forskolin, an adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activator, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC)-activating phorbol ester, enhanced these cytokine-induced reactions. These results indicate that iNOS expression by cytokines is mediated via a protein tyrosine kinase-dependent pathway and is positively modulated by both PKA- and PKC-dependent pathways in this cell type.

MeSH terms

  • Animals
  • Cell Line
  • Enzyme Activation
  • Enzyme Induction
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / enzymology*
  • Nitric Oxide Synthase / metabolism*
  • Nitrites / metabolism
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rats
  • Recombinant Proteins
  • Time Factors

Substances

  • Interleukin-1
  • Nitrites
  • Recombinant Proteins
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Protein Kinases
  • Protein-Tyrosine Kinases