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

• 来源期刊: 中国药理学报（英文版）
• 关键词: cardiac hypertrophy signal transduction cardiotrophin-1 MAP kinase signaling system transactivators 1-phosphatidylinositol 3-kinase
• 年，卷（期）: 2004,（9）
• 页码范围: 1157-1164
• 页数: 8页
• 语种: 英文

摘要

AIM: To assess the contribution of signal transducer and activator of transcription 3 (JAK-STAT3) pathway,extracellular signal-regulated kinases 1/2 (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. METHODS: STAT3, ERK1/2, and PI3-K were assessed by Western blot analysis. Activity of ERK1/2was also confirmed by in-gel kinase assay. Hypertrophy of cardiomyocyte was evaluated by [3H]leucine incorporation and cellular protein-to-DNA ratio. RESULTS: CT-1 simultaneously activated phosphorylation of STAT3,ERK1/2, and PI3-K in rat cardiomyocytes. Parthenolide, an inhibitor of STAT, suppressed CT-l-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-toDNA ratio. CONCLUSION: The hypertrophic effect of CT-1 was essentially mediated by STAT3, independent of PI3-K, and negatively regulated by ERK1/2 via inhibiting the phosphorylation of STAT3. The interaction between STAT3 and ERK1/2 in CT-l-induced signaling contributes to development of cardiac hypertrophy.