Key result
TAK733 significantly reduced norepinephrine- and phenylepinephrine-induced cardiomyocyte hypertrophy by regulating ERK1/2 and ERKThr188 activation and depressing MEK activity.
Why the study?
The MEK-ERK axis regulates cardiac hypertrophy, and the authors investigated whether the selective MEK inhibitor TAK733 exerts anti-hypertrophic effects in cardiomyocytes.
Does TAK733 reduce norepinephrine- or phenylephrine-induced cardiomyocyte hypertrophy in H9c2 cells?
Does TAK733 reduce norepinephrine- or phenylephrine-induced cardiomyocyte hypertrophy in H9c2 cells?
TAK733 attenuates adrenergic receptor-mediated cardiomyocyte hypertrophy in vitro, suggesting potential as a therapeutic agent for cardiac hypertrophy.
May support preclinical MEK inhibition in hypertrophy models; leaves open any clinical translation to heart failure prevention.
BACKGROUND: Cardiac hypertrophy is an important risk factor for heart failure. The MEK-ERK axis has been reported as a major regulator in controlling cardiac hypertrophy. TAK733 is a potent and selective MEK inhibitor that suppresses cell growth in a broad range of cell lines. OBJECTIVE: Therefore, we aimed to investigate the anti-hypertrophic effect of TAK733 in cardiomyocytes. METHODS: Cardiomyocyte hypertrophy was induced with norepinephrine (NE) or phenylepinephrine (PE) using H9c2 cells. To confirm the cardiomyocyte hypertrophy, cell size and protein synthesis were measured and hypertrophy-related gene expression was estimated by reverse transcription polymerase chain reaction. To identify the signaling pathway involved, immunoblot analysis were performed. RESULTS: We observed that NE activated MEK-ERK signaling and increased ANP and BNP expression, resulting in cardiomyocyte hypertrophy. TAK733 significantly reduced cardiomyocyte hypertrophy by regulating NE-induced ERK1/2 and ERKThr188 activation, hypertrophy marker expression, and cardiomyocyte hypertrophy through depression of MEK activity. In addition, we examined that PE-induced cardiomyocyte hypertrophy was also attenuated by TAK733. CONCLUSIONS: Here, we report that TAK733 suppressed NE- or PE-induced cardiomyocyte hypertrophy by repressing a crucial component of cardiac hypertrophy-related pathways. These results suggest that TAK733 may be a useful therapeutics for cardiac hypertrophy and warrants further in vivo studies.
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Lee et al. (2019) studied Cardiac hypertrophy. TAK733 vs. Norepinephrine or phenylepinephrine alone was evaluated on Cardiomyocyte hypertrophy (cell size, protein synthesis, and hypertrophy-related gene expression). TAK733 significantly reduced norepinephrine- and phenylepinephrine-induced cardiomyocyte hypertrophy by regulating ERK1/2 and ERKThr188 activation and depressing MEK activity.
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