Expression of mitochondrial fusion–fission proteins during post-infarction remodeling: the effect of NHE-1 inhibition
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Sabzali Javadov Venkatesh Rajapurohitam Ana Kilic´ J. Craig Hunter Asad Zeidan Nazo Said Faruq Nelson Escobales Morris Karmazyn
- چاپ و سال / کشور: 2010
Description
Studies on the role of mitochondrial fission/ fusion (MFF) proteins in the heart have been initiated recently due to their biological significance in cell metabolism. We hypothesized that the expression of MFF proteins is affected by post-infarction remodeling and in vitro cardiomyocyte hypertrophy, and serves as a target for the Na?/H? exchanger 1 (NHE-1) inhibition. Post-infarction remodeling was induced in Sprague–Dawley rats by coronary artery ligation (CAL) while in vitro hypertrophy was induced in cardiomyocytes by phenylephrine (PE). Mitochondrial fission (Fis1, DRP1) and fusion (Mfn2, OPA1) proteins were analyzed in heart homogenates and cell lysates by Western blotting. Our results showed that 12 and 18 weeks after CAL, Fis1 increased by 80% (P\0.01) and 31% (P\0.05), and Mfn2 was reduced by 17% (P\0.05) and 22% (P\0.05), respectively. OPA1 was not changed at 12 weeks, although its expression decreased by 18% (P\0.05) with 18 weeks of ligation. MFF proteins were also affected by PE-induced hypertrophy that was dependent on mitochondrial permeability transition pore opening and oxidative stress. The NHE-1-specific inhibitor EMD-87580 (EMD) attenuated changes in the expression of MFF proteins in both the models of hypertrophy. The effect of EMD was likely mediated, at least in part, through its direct action on mitochondria since Percoll-purified mitochondria and mitoplasts have been shown to contain NHE-1. Our study provides the first evidence linking cardiac hypertrophy with MFF proteins expression that was affected by NHE-1 inhibition, thus suggesting that MFF proteins might be a target for pharmacotherapy with anti-hypertrophic drugs.
Basic Res Cardiol (2011) 106:99–109 Received: 16 March 2010 / Revised: 1 September 2010 / Accepted: 19 September 2010 / Published online: 1 October 2010
