The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes

Gillespie-Brown, J; Fuller, S; Bogoyevitch, M; Cowley, S; Sugden, P

Journal article

The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes

Abstract:: Adult mammalian ventricular cardiomyocytes are terminally differentiated cells that enlarge adaptively by hypertrophy. In this situation, genes normally expressed in the fetal ventricular cardiomyocyte (e.g. atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), and skeletal muscle (SkM) alpha-actin) are re-expressed, and there is transient expression of immediate early genes (e.g. c-fos). Using appropriate reporter plasmids, we studied the effects of transfection of the constitutively active or dominant negative mitogen-activated protein kinase kinase MEK1 on ANF, beta-MHC, and SkM alpha-actin promoter activities in cultured ventricular cardiomyocytes. ANF expression was stimulated (maximally 75-fold) by the hypertrophic agonist phenylephrine in a dose-dependent manner (EC50, 10 microM), and this stimulation was inhibited by dominant negative MEK1. Cotransfection of dominant negative MEK1 with a dominant negative mitogen-activated protein kinase (extracellular signal-regulated protein kinase (ERK2)) increased this inhibition. Transfection with constitutively active MEK1 constructs doubled ANF promoter activity. The additional cotransfection of wild-type ERK2 stimulated ANF promoter activity by about 5-fold. Expression of beta-MHC and SkM alpha-actin was also stimulated. Promoter activity regulated by activator protein-1 or c-fos serum response element consensus sequences was also increased. We conclude that the MEK1/ERK2 cascade may play a role in regulating gene expression during hypertrophy.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Gillespie-Brown, J., Fuller, S., Bogoyevitch, M., Cowley, S., & Sugden, P. (1995). The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. Journal of Biological Chemistry, 270(47), 28092–28096.

MLA Style

Gillespie-Brown, J, et al. “The Mitogen-Activated Protein Kinase Kinase MEK1 Stimulates a Pattern of Gene Expression Typical of the Hypertrophic Phenotype in Rat Ventricular Cardiomyocytes.” Journal of Biological Chemistry, vol. 270, no. 47, 1995, pp. 28092–96.

Chicago Style

Gillespie-Brown, J, S Fuller, M Bogoyevitch, S Cowley, and P Sugden. 1995. “The Mitogen-Activated Protein Kinase Kinase MEK1 Stimulates a Pattern of Gene Expression Typical of the Hypertrophic Phenotype in Rat Ventricular Cardiomyocytes.” Journal of Biological Chemistry 270 (47): 28092–96.
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