Glycogen Synthase Kinase-3β is Involved in the Process of Myocardial Hypertrophy Stimulated by Insulin-Like Growth Factor-1

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Background Glycogen synthase kinase-3β (GSK-3β) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3β in some cell types. The role of GSK-3β in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3β in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. Methods and Results First, the IGF-1 induced signal transduction leading to GSK-3β in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3β signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3β acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3β (Ad GSK-3β S9A) repressed these hypertrophic effects of IGF-1. Conclusion GSK-3β may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1.
社団法人日本循環器学会の論文
2004-02-20

Glycogen Synthase Kinase-3β is Involved in the Process of Myocardial Hypertrophy Stimulated by Insulin-Like Growth Factor-1

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