Reduced troponin I phosphorylation and increased Ca(2+)-dependent ATP-consumption in triton X-skinned fiber preparations from Galphaq overexpressor mice.
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| Abstract |
Overexpression of the Galphaq-protein has been shown to result in hypertrophic and dilated cardiomyopathy. This study investigated Ca(2+ )sensitivity of tension and myosin-ATPase activity in skinned fiber preparations of male and female wildtype (WT; n = 12) and transgenic mice with a cardiac specific overexpression of the Galphaq-protein (Galphaq-OE; n = 11). In addition, the phosphorylation status of troponin I was measured. Ca(2+) sensitivity of tension was increased in Galphaq-OE with a significant reduction in the half-maximum Ca(2+) concentration (EC(50)) compared to WT. Similarly, Ca(2+) sensitivity of myosin ATPase activity was increased in Galphaq-OE when comparing Galphaq-OE to WT. Maximum Ca(2+)-dependent tension and ATPase activity were both enhanced in Galphaq-OE compared to WT littermates. Phosphorylation of troponin I was significantly reduced in Galphaq-OE compared to WT. In the above experiments, no gender specific differences were observed in either Gaq-OE or in WT. We conclude that, in mice, increased expression of the Galphaq-protein induces alterations of myofibrillar function and energy consumption, which are also characteristics of human heart failure. This may result from a decreased phosphorylation of troponin I in Galphaq-OE.
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| Authors | C Pott, L Willkomm, S Grafweg, B Bölck, G W Dorn 2nd, R H G Schwinger, K Brixius |
| Journal | Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 314 Issue 1-2 Pg. 133-41 (Jul 2008) ISSN: 0300-8177 [Print] Netherlands |
| PMID | 18473122 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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