Regulation of inducible nitric oxide synthase expression in l6 rat
skeletal muscle cells.
Okuda, S., F. Kanda, Y. Kawahara, and K. Chihara.
Third Division, Department of Medicine, Kobe University School of
Medicine, First Division, Department of Medicine, Kobe University
School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan
APStracts 3:0248C, 1996.
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 NO. 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, a cAMP-dependent protein kinase (PKA)
-activator, and phorbol 12-myristate 13-acetate, a protein kinase C
(PKC)-activating phorbol ester, enhanced cytokine-induced these
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.
Received 11 April 1996; accepted in final form 10 July 1996
APS Manuscript Number C199-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996