When heart muscle cells are put under stress, for example by high blood pressure or by oxygen deprivation (such as occurs during a heart attack), they switch from using fatty acids as their source of energy to using glucose.
Robb MacLellan and colleagues, at the David Geffen School of Medicine at UCLA, have now generated several lines of evidence to indicate that the gene regulatory protein Myc is responsible for inducing the expression of the genes involved in using glucose as an energy source in mice and that this helps protect the heart from stress.
Initial analysis by the authors indicated that expression of Myc was increased in the hearts of mice under conditions that model high blood pressure as well as conditions that model the oxygen deprivation associated with a heart attack. Furthermore, increasing Myc expression in the heart in the absence of any stress condition made the heart muscle cells switch from fatty acids to glucose as their source of energy.
Importantly, the Myc-mediated switch to using glucose as an energy source was associated with preserving heart function and improving recovery from oxygen deprivation. Thus, Myc has an important adaptive role in the mouse heart, equipping it with an enhanced ability to respond to oxygen deprivation.
The research appears in the Journal of Clinical Investigation.
- Preeti Ahuja, Peng Zhao, Ekaterini Angelis, Hongmei Ruan, Paavo Korge, Aaron Olson, Yibin Wang, Eunsook S. Jin, F. Mark Jeffrey, Michael Portman and W. Robb Maclellan. Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI38331
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