Nitric oxide inhibits the expression of proto-oncogene c-fos induced by angiotensin II and endothelin-1 in cardiomyocytes.
The effect of nitric oxide (NO) on the hypertrophic response and the proto-oncogene c-fos expression induced by angiotensin II (AII) or endothelin-1 (ET-1) was investigated in the primary culture of neonatal rat cardiomyocytes. Total protein content of cardiomyocytes (used as the index of cardiac myocyte hypertrophy) was determined by the Bradford method. The proto-oncogene c-fos expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR) standardized with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RT-PCR was performed in a single tube using gene-specific primers and the SuperScript One-Step RT-PCR System. Total protein content of cardiomyocytes increased significantly on day 5 after A II treatment or on day 3 after ET-1 treatment and the increased protein content was inhibited by SNP (NO donor). A II, ET-1 and PMA (protein kinase C activator) induced the c-fos gene expression of cardiomyocytes, while L-arginine inhibited it. The L-arginine effect was blocked by L-NAME (NOS inhibitor). SNP inhibited the c-fos gene expression of cardiomyocytes induced by A II,ET-1 or PMA as well. These results suggest that NO can inhibit the hypertrophic response and the proto-oncogene c-fos expression of cardiomyocytes induced by A II or ET-1 and the cross-link may be located at the site of protein kinase C.
Zhan
C D
CD
Key Laboratory of the Ministry of Health on Assisted Circulation, Department of Physiology, Sun Yat-sen University of Medical Sciences, Guangzhou 510089.
Pan
J Y
JY
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D016760:Proto-Oncogene Proteins c-fos; D000804:Angiotensin II; D009569:Nitric Oxide