Hypertrophy-associated gene induction after beta-adrenergic stimulation inadult cardiomyocytes

In isolated cardiomyocytes, hypertrophic responsiveness to beta -adrenergic stimulation can be induced by pre-exposure of the cells to TGF-beta. To ch aracterize genes involved in beta -adrenergically mediated hypertrophy, mRN A expression patterns in isoprenaline-stimulated cardiomyocytes which were pre-exposed to TGF-beta were analysed by differential display RT-PCR analys is. Eighteen fragments, upregulated by isoprenaline, were identified, Six o f them, which code for proteins with known function, were further analysed by RT-PCR (1) to verify their induction after beta -adrenergic stimulation, (2) to restrict their number to genes only upregulated after hypertrophy i nducing beta -adrenergic stimulation, and (3) to study their expression in stroke-prone spontaneous hypertrophic rats (SHR-sp), an in vivo model of my ocardial hypertrophy, in which elevated levels of TGF-beta are found. Induc tion by isoprenaline could be proved for all but one of the six genes. Furt her analysis of these genes in Freshly isolated myocytes, which respond wit h hypertrophic growth only to alpha- but not beta -adrenergic stimulation, revealed that three of them, coding for the translation initiation factor s ui 1, the cis-golgi transport protein p28 and the mitochondrial NADH-dehydr ogenase II subunit, are specifically induced in TGF-beta -pre-exposed cardi omyocytes after beta -adrenergic stimulation. Their induction is therefore closely associated with a beta -adrenergic growth response in isolated card iomyocytes. p28-mRNA is also markedly increased in SHR-sp rats. Antisense e xperiments revealed a functional importance of p28 for the beta -adrenergic growth response in isolated cardiomyocytes, Therefore, p28 seems causally involced in this beta -adrenergic grow ih response, (C) 2001 Academic Press .