Mechanical strain suppresses inducible nitric-oxide synthase in cardiac myocytes.
J Biol Chem
; 273(19): 11862-6, 1998 May 08.
Article
em En
| MEDLINE
| ID: mdl-9565611
ABSTRACT
We investigated the effects of precisely controlled mechanical strain on nitric-oxide synthase activity in cultured neonatal rat cardiac myocytes. Incubation of cardiac myocytes for 24 h with 4 ng/ml interleukin-1beta and 100 units/ml interferon-gamma stimulated an increase in nitric oxide production, inducible nitric-oxide synthase (iNOS) mRNA, and iNOS protein. Mechanical strain suppressed nitric oxide production, iNOS mRNA, and iNOS protein stimulated by cytokines in an amplitude-dependent manner. Losartan (1 microM), an angiotensin II type 1 receptor antagonist, weakly inhibited the effect of strain, suggesting that paracrine angiotensin II is not the mediator of the strain effect. In addition, cycloheximide (10 microM), a protein synthesis inhibitor, inhibited the effect of strain by 46%. Transforming growth factor-beta (1 ng/ml) suppressed iNOS mRNA expression, but anti-transforming growth factor-beta antibody (30 microg/ml) did not block the effect of strain. In contrast, staurosporine (100 nM; a nonselective protein kinase inhibitor), calphostin C (1 microM; a selective protein kinase C inhibitor), and pretreatment with phorbol 12-myristate 13-acetate abolished the effect of strain. Genistein (100 microM), a tyrosine kinase inhibitor, partially inhibited the effect of strain. Thus, cyclic mechanical deformation suppresses cytokine-induced iNOS expression in cardiac myocytes, and this effect is mediated at least partially via activation of protein kinase C.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Óxido Nítrico Sintase
/
Miocárdio
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos