Study Findings from Medical Academy Broaden Understanding of Small Interference RNAs (siRNAs) (Inhibition of MMP-2 expression affects metabolic enzyme expression levels: Proteomic analysis of rat cardiomyocytes)
By a News Reporter-Staff News Editor at Biotech Week -- New research on Small Interference RNAs (siRNAs) is the subject of a report. According to news reporting from Wroclaw, Poland, by NewsRx journalists, research stated, "In this study we examined the effect of inhibition of MMP-2 expression, using siRNA, on the cardiomyocyte proteome. Isolated cardiomyocytes were transfected with MMP-2 siRNA and incubated for 24 h. Control cardiomyocytes from the same heart were transfected with scrambled siRNA following the same protocol."
The news correspondents obtained a quote from the research from Medical Academy, "Comparison of control cardiomyocyte proteomes with proteomes from MMP-2 suppressed cardiomyocytes revealed 13 protein spots of interest (9 protein spots increased; 4 decreased). Seven protein spots were identified as mitochondrial enzymes involved in energy production and represent: ATP synthase beta subunit, dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, cytochrome c oxidase subunit 5A, electron transfer flavoprotein subunit beta, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 5 and a fragment of mitochondrial precursor of long-chain specific acyl-CoA dehydrogenase. Furthermore, precursor of heat shock protein 60 and Cu-Zn superoxide dismutase were identified. Two protein spots corresponding to MLC1 were also detected. In addition, ATP synthase activity was measured and was increased by approximately 30%. Together, these results indicate that MMP-2 inhibition represents a novel cardioprotective therapy by promoting alterations in the levels of mitochondrial enzymes for improved energy metabolism and by preventing degradation of contractile proteins needed for normal excitation contraction coupling. Biological significance During ischemia and reperfusion of cardiomyocytes, abnormality in excitation contraction coupling and decreased energy metabolism often lead to myocardial infarction, but the cellular mechanisms are not fully elucidated. We show for the first time that intracellular inhibition of MMP-2 in cardiomyocytes increases contractility of aerobically perfused myocytes, which was accompanied by increased expression of contractile proteins (e.g., MLC-1). We also showed that MMP-2 inhibition produced a cardiomyocyte proteome that is consistent with improved mitochondrial energy metabolism (e.g., increased expression and activity of mitochondrial beta ATP synthase). Thus, MMP-2 appears to be involved in homeostatic regulation of protein turnover. Our results are significant since they point to targeting MMP-2 activity as a novel therapeutic option to limit myocardial damage by decreasing proteolytic degradation of mitochondrial metabolic enzymes and myocardial contractile proteins during ischemia."
According to the news reporters, the research concluded: "In addition, the development of novel pharmacological agents that selectively targets cardiac MMP-2 represents a novel approach to treat and prevent other heart diseases."
For more information on this research see: Inhibition of MMP-2 expression affects metabolic enzyme expression levels: Proteomic analysis of rat cardiomyocytes. Journal of Proteomics, 2014;106():74-85. Journal of Proteomics can be contacted at: Elsevier Science Bv, PO Box 211, 1000 Ae Amsterdam, Netherlands. (Elsevier - www.elsevier.com; Journal of Proteomics - www.elsevier.com/wps/product/cws_home/713351)
Our news journalists report that additional information may be obtained by contacting H.B. Lin, Medical Academy Wroclaw, Dept. of Clin Chem, Wroclaw, Poland. Additional authors for this research include K. Sharma, D. Bialy, M. Wawrzynska, R. Purves, F.S. Cayabyab, M. Wozniak and G. Sawicki (see also Small Interference RNAs (siRNAs)).
Keywords for this news article include: Poland, Europe, Wroclaw, Genetics, Synthase, Cardiology, Proteomics, Cardiomyocyte, Dehydrogenase, Enzymes and Coenzymes, Small Interference RNAs (siRNAs)
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