caa a22 4500 606233660 CHVBK 20210128101233.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2380-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2380-8 Na+/H+ exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4 [Elektronische Daten] [Mohamed Mlih, Nabeel Abdulrahman, Alain-Pierre Gadeau, Iman Mohamed, Maiy Jaballah, Fatima Mraiche] Osteopontin (OPN), a multifunctional glycophosphoprotein, has been reported to contribute to the development and progression of cardiac remodeling and hypertrophy. Cardiac-specific OPN knockout mice were protected against hypertrophy and fibrosis mediated by Ang II. Recently, transgenic mice expressing the active form of the Na+/H+ exchanger isoform 1 (NHE1) developed spontaneous hypertrophy in association with elevated levels of OPN. The mechanism by which active NHE1 induces OPN expression and contributes to the hypertrophic response remains unclear. To validate whether expression of the active form of NHE1 induces OPN, cardiomyocytes were stimulated with Ang II, a known inducer of both OPN and NHE1. Ang II induced hypertrophy and increased OPN protein expression (151.6±28.19%, P<0.01) and NHE1 activity in H9c2 cardiomyoblasts. Ang II-induced hypertrophy and OPN protein expression were regressed in the presence of an NHE1 inhibitor, EMD 87580, or a calcineurin inhibitor, FK506. In addition, our results indicated that activation of NHE1-induced NFAT3 translocation into the nucleus and a significant activation of the transcription factor Gata4 (NHE1: 149±28% of control, P<0.05). NHE1-induced activation of Gata4 was inhibited by FK506. In summary, our results suggest that activation of NHE1 induces hypertrophy through the activation of NFAT3/Gata4 and OPN expression. Springer Science+Business Media New York, 2015 Cardiomyocyte hypertrophy nationallicence Na+/H+ exchanger isoform 1 nationallicence Osteopontin nationallicence H9c2, NFAT3, Gata4 nationallicence NHE1 : Na+/H+ exchanger isoform 1 nationallicence OPN : Osteopontin nationallicence NFAT : Nuclear factor of activated T-cells nationallicence ANP : Atrial natriuretic peptide nationallicence ERK : Extracellular signal regulated kinase nationallicence Ang II : Angiotensin II nationallicence Mlih Mohamed College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut Abdulrahman Nabeel College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut Gadeau Alain-Pierre INSERM U441, Bordeaux, France aut Mohamed Iman College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut Jaballah Maiy College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut Mraiche Fatima College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 211-220 0300-8177 404:1-2<211 2015 404 11010 https://doi.org/10.1007/s11010-015-2380-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2380-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mlih Mohamed College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut NATIONALLICENCE 700 1- Abdulrahman Nabeel College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut NATIONALLICENCE 700 1- Gadeau Alain-Pierre INSERM U441, Bordeaux, France aut NATIONALLICENCE 700 1- Mohamed Iman College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut NATIONALLICENCE 700 1- Jaballah Maiy College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut NATIONALLICENCE 700 1- Mraiche Fatima College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 211-220 0300-8177 404:1-2<211 2015 404 11010