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Mechanical Strain Increases Expression of the Brain Natriuretic Peptide Gene in Rat Cardiac Myocytes

Liang, Faquan and Wu, Jianming and Garami, Miklós and Gardner, D. G. (1997) Mechanical Strain Increases Expression of the Brain Natriuretic Peptide Gene in Rat Cardiac Myocytes. Journal of Biological Chemistry, 272 (44). pp. 28050-28056. ISSN 0021-9258 (print) 1083-351X (online)

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Abstract

Using a device that applies cyclical strain (1 Hz) to ventricular cardiocytes cultured on collagen-coated silicone elastomer surfaces, we have demonstrated strain-dependent increases in brain natriuretic peptide (BNP) secretion, BNP mRNA levels, and expression of a transiently transfected -1595 human BNP-luciferase reporter. When actinomycin D (10 mu M) was introduced concomitantly with the strain stimulus, the strain-induced increase in BNP mRNA was eliminated, and the decay of transcripts was identical in the control and strained cells, indicating the lack of independent effects on transcript stability. Strain-dependent -1595 human BNP-luciferase activity was completely inhibited by chelerythrine, a-aminopurine, genistein, and W-7 and only partially or not at all by KN-62, wortmannin, and H-89. The effects of these individual agents paralleled their effects on mitogen-activated protein kinase (MAPK) activity, but not c-Jun N-terminal kinase (JNK) activity, in the cells. Overexpression of wild-type MAPK and, to a lesser extent, JNK increased strain-dependent BNP promoter activity, whereas dominant-negative mutants of MAPK kinase, JNK kinase, or Ras completely blocked strain-dependent reporter activity. These findings provide the first demonstration that mechanical strain can increase myocardial gene expression through a transcriptional mechanism and suggest important roles for MAPK and JNK in mediating this effect.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: Erika Bilicsi
Date Deposited: 04 Jan 2013 13:10
Last Modified: 04 Jan 2013 13:10
URI: http://real.mtak.hu/id/eprint/3776

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