p90 Ribosomal S6 Kinase Contributes to Na+/H+ Exchanger Isoform1 (NHE1) Induced Cardiac Hypertrophy in H9c2 Cardiomyoblasts Maiy Jaballah, Bayan Almerayat, Fatima Al-Sulaiti, Fatima Mraiche College of Pharmacy, Qatar University, Doha, Qatar Background Pharmacological and genetical studies have shown that increasing the activity of Na+/H+ exchanger isoform1 (NHE1) plays a critical role in the development of cardiac hypertrophy. Despite the importance of NHE1, direct inhibition of NHE1 has demonstrated several adverse side effects. It is has been demonstrated that p90 ribosomal S6 kinase (RSK) enhances the activity of NHE1. RSK, a downstream regulator of the mitogen activated pathway, has also been implicated in cardiac hypertrophy both in in vitro and in vivo models. The aim of this study is to investigate the cardio protective effects mediated by inhibition of RSK in NHE1 activated cells. Methods In vitro, H9c2 cardiomyoblasts are infected with active NHE1 adenovirus in the absence and presence of dominant negative (Dn) RSK2 (N-terminal kinase dead protein) adenovirus. H9c2 cardiomyoblasts expressing active NHE1 with abolished RSK activity are characterized for cardiac hypertrophy by measuring cell area and protein content. Results Our results showed that infection of H9c2 cells with active NHE1 adenovirus resulted in significant increase in cell area, (NHE1: 154.5±28.47% of GFP), which was reduced by concomitant infection with Dn RSK2 (NHE1+Dn RSK2: 137.4±11.8% of GFP). Similarly, protein content induced by active NHE1 was attenuated in the presence Dn RSK2. Conclusion Taken together, our study demonstrates that active NHE1 induces cardiac hypertrophy. Inhibition of active NHE1 by targeting RSK may regress the hypertrophic effect, thus making RSK a potential therapeutic target for cardiac hypertrophy.


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