Na+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiomyocyte hypertrophy

View/ Open
Date
2015-04Author
Mohamed, Iman A.Gadeau, Alain-Pierre
Fliegel, Larry
Lopaschuk, Gary
Mlih, Mohamed
Abdulrahman, Nabeel
Fillmore, Natasha
Mraiche, Fatima
...show more authors ...show less authors
Metadata
Show full item recordAbstract
Enhanced expression and activity of the Na+/H+ exchanger isoform 1 (NHE1) has been implicated in cardiomyocyte hypertrophy in various experimental models. The upregulation of NHE1 was correlated with an increase in osteopontin (OPN) expression in models of cardiac hypertrophy (CH), and the mechanism for this remains to be delineated. To determine whether the expression of active NHE1-induces OPN and contributes to the hypertrophic response in vitro, cardiomyocytes were infected with the active form of the NHE1 adenovirus or transfected with OPN silencing RNA (siRNA-OPN) and characterized for cardiomyocyte hypertrophy. Expression of NHE1 in cardiomyocytes resulted in a significant increase in cardiomyocyte hypertrophy markers: cell surface area, protein content, ANP mRNA and expression of phosphorylated-GATA4. NHE1 activity was also significantly increased in cardiomyocytes expressing active NHE1. Interestingly, transfection of cardiomyocytes with siRNA-OPN significantly abolished the NHE1-induced cardiomyocyte hypertrophy. siRNA-OPN also significantly reduced the activity of NHE1 in cardiomyocytes expressing NHE1 (68.5±0.24%; P<0.05), confirming the role of OPN in the NHE1-induced hypertrophic response. The hypertrophic response facilitated by NHE1-induced OPN occurred independent of the extracellular-signal-regulated kinases and Akt, but required p90-ribosomal S6 kinase (RSK). The ability of OPN to facilitate the NHE1-induced hypertrophic response identifies OPN as a potential therapeutic target to reverse the hypertrophic effect induced by the expression of active NHE1.
Collections
- Pharmacy Research [405 items ]
Related items
Showing items related by title, author, creator and subject.
Title | Author | Publication Date | Publisher | Type |
---|---|---|---|---|
Effects of the P20 protein from Bacillus thuringiensis israelensis on insecticidal crystal protein Cry4Ba | Jaoua, Samir | 2015 | Elsevier B.V. | Article |
Protein expression profiling identifies key proteins and pathways involved in growth inhibitory effects exerted by guggulsterone in human colorectal cancer cells | Leo R.; Therachiyil L.; Siveen S.K.; Uddin S.; Kulinski M.; Buddenkotte J.; Steinhoff M.; Krishnankutty R.... more authors ... less authors | 2019 | MDPI AG | Article |
Role of Proteinases in the Degradation of the Major Storage Proteins of Linseed Germinating Seeds Alternative Title: دور أنزيمات التحلل البروتيني في هدم البروتينات المخزنة في يذور الكتان النامية | Sammour, Reda Helmy [رضا حلمي سمور] | 1999 | Qatar University | Article |