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- W1520563278 abstract "Mitogen activated protein kinases (MAPKs) play an important role in cell grow, proliferation and apoptosis in the heart. The MAPK family involves three major subgroups including extracellular signal-regulated protein kinase (ERK1/2), p38, and c-jun N-terminal kinases (JNK). Despite many studies demonstrating anti-hypetrophic action of AMP-kinase (AMPK), a metabolic sensor regulating energy metabolism, the relationship between AMPK activation and MAPKs is not clear yet. We hypothesize that beneficial effects of AMPK are mediated, at least in part, through modification of MAPKs activation. Experiments were performed on H9c2 myoblastic rat cardiomyocytes incubated at 370C with 95% air and 5% CO2. Hypertrophy was induced by treatment of the cells with 200 nM angiotensin II (Ang II, a peptide hormone stimulating hypertrophy) or 10 μM phenylephrine (PE, the α1-adrenergic receptor agonist). First, we determined time-course activation (phosphorylation) of ERK1/2, p38 and JNK in response to Ang II and PE. Second, we evaluated, if activation/inhibition of AMPK by metformin/compound C influences activation of the MAPKs induced by AngII or PE. Results demonstrated that maximum activation of all three MAPKs occurs at 10 min after addition of the hypertrophic agents. A time point of 10 min was selected to determine whether AMPK affects MAPKs activation in AngII-treated cells. Metformin (2 mM) or compound C (10 μM) was added to the culture medium 45 min before AngII or PE treatment. Metformin significantly abrogated the activation of all three MAPKs induced by AngII or PE. Inhibition of AMPK by compound C had no effect on MAPK phosphorylation suggesting that the effects are mediated via AMPK. Surprisingly, losartan had no significant effects on MAPK activation in AngII-treated cells. In conclusion, our findings demonstrate that ERK1/2, p38 and JNK MAPKs play a crucial role in mediating anti-hypertrophic effects of AMPK in cardiomyocyte hypertrophy. Grant Funding Source: Supported by the NHLBI NIH grant SC1HL118669 (S.J.) and APS/NHLBI STRIDE Summer Research Fellowship" @default.
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- W1520563278 date "2014-04-01" @default.
- W1520563278 modified "2023-10-06" @default.
- W1520563278 title "The role of p38, ERK1/2 and JNK mitogen activated protein kinase in the anti‐hypertrophic action of AMP‐kinase in cardiomyocytes (1097.13)" @default.
- W1520563278 doi "https://doi.org/10.1096/fasebj.28.1_supplement.1097.13" @default.
- W1520563278 hasPublicationYear "2014" @default.
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