HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy

• Published in: The Journal of biological chemistry Vol. 268; no. 3; pp. 2244 - 2249
• Main Authors: THORBURN, A, THORBURN, J, SEI-YU CHEN, POWERS, S, SHUBEITA, H. E, FERAMISCO, J. R, CHIEN, K. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-01-1993
• Subjects: Animals; Animals, Newborn; Atrial Natriuretic Factor - genetics; Biological and medical sciences; Cardiomegaly - genetics; Cell Division; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression - physiology; Genes, fos; Genes, ras - physiology; Genetic Markers; Heart Ventricles - cytology; Molecular and cellular biology; Myocardium - cytology; Phenylephrine - pharmacology; Rats; Responses to growth factors, tumor promotors, other factors; Transfection; Heart; Vertebrata; Mammalia; Rat; C-Onc gene; Rodentia; Atrial natriuretic peptide; Gene expression; Hypertrophy; Myocyte
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)53988-0

We have investigated the role of the proto-oncogene HRas in cardiac cell growth and hypertrophy. By direct needle microinjection
of activated Ras protein into primary neonatal rat ventricular cardiac myocytes, we find that, unlike many other cell types,
Ras does not induce DNA synthesis in these cells. However, injection of activated Ras does induce expression of both the c-Fos
and atrial natriuretic factor (ANF) genes. Expression of both these genes is associated with the hypertrophic response in
ventricular myocytes suggesting that Ras is involved in the hypertrophic signalling pathway. Ras injection also causes morphological
changes in the cells so that they increase in profile and show changes in the organization of the contractile apparatus. Further
support for a role for Ras in the hypertrophic response was obtained from studies showing that activated Ras stimulates ANF
promoter activity in transient transfection assays. We also show that a dominant interfering Ras mutant inhibits the hypertrophic
stimulation of the ANF promoter by phenylephrine, indicating a role for Ras in the hypertrophic effect of an alpha-adrenergic
agonist.