PMID: 15339391Sep 2, 2004Paper

Different contributions of STAT3, ERK1/2, and PI3-K signaling to cardiomyocyte hypertrophy by cardiotrophin-1

Acta Pharmacologica Sinica
Ze-Jun TianWei An

Abstract

To assess the contribution of signal transducer and activator of transcription 3 (JAK-STAT3) pathway, extracellular signal-regulated kinases1/2 (ERK1/2) pathway, and phosphatidylinositol 3-kinase (PI3-K) pathway to cardiomyocytes hypertrophy induced by cardiotrophin-1 (CT-1), a new member of interleukin-6 (IL-6) family of cytokines. STAT3, ERK1/2, and PI3-K were assessed by Western blot analysis. Activity of ERK1/2 was also confirmed by in-gel kinase assay. Hypertrophy of cardiomyocyte was evaluated by [3H]leucine incorporation and cellular protein-to-DNA ratio. CT-1 simultaneously activated phosphorylation of STAT3, ERK1/2, and PI3-K in rat cardiomyocytes. Parthenolide, an inhibitor of STAT, suppressed CT-1-induced [3H]leucine incorporation by 88.3 % and protein-to-DNA ratio by 75.0 %. U0126, an MEK1/2 inhibitor, increased CT-1-induced the phosphorylation of STAT3 in a dose-dependent manner and, consistently, augmented CT-1-induced increase in [3H]leucine incorporation and cellular protein-to-DNA ratio by 17.6 % and 16.3 %, respectively. Wortmannin, a PI3-K inhibitor, did not influence CT-1-induced [3H]leucine incorporation and cellular protein-to-DNA ratio. The hypertrophic effect of CT-1 was essentially mediated by STAT3, in...Continue Reading

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