PITTSBURGHResearchers from the University of Pittsburgh and the University of Chicago were able to control heart muscle function in a new way after discovering the previously unknown role of two enzymes in heart muscle contraction, as detailed in the April 11 cover story of the Journal of Biological Chemistry. Although in the early stages, the research provides fresh knowledge of how heart muscle functions and also holds early potential as a treatment for various heart diseasesincluding congestive heart failurethat is possibly less taxing on the heart than current regimens.
Experiments on slivers of heart muscle revealed that heart muscle contractions can be regulated by the enzymes histone acetyltransferases (HATs) and histone deacetylases (HDACs), explained Pitt professor Sanjeev Shroff, the Gerald McGinnis Chair of Bioengineering in the Swanson School of Engineering. Shroff and Pitt research associate Stephen Smith collaborated with Mahesh Gupta, an associate professor of surgery at the University of Chicago, and his research associate Sadhana Samant. The project was funded by a grant from the National Institutes of Health.
The team found that HATs and HDACs influence acetylation of certain heart muscle proteins, a process wherein a radical cluster of atoms called an acetyl group attach to a protein and change its function. HATs facilitate acetylation, and HDACs remove the acetyl group. The team discovered that acetylation renders the muscle fiber more sensitive to calcium, which causes the muscle to contract.
This is a completely new process in the area of heart muscle contraction, Shroff said. Acetylation is widely known to regulate such events inside the cell nucleus as gene regulation, but its never before been associated with heart muscle contraction.
Furthermore, Shroff and his colleagues could intervene in this microscopic process to control heart muscle contraction. By inhibiting HDACs, they increased the calcium s
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University of Pittsburgh