It was led by Walter J. Koch, Ph.D., Professor and Chairman of the Department of Pharmacology at TUSM, and Director of the Center for Translational Medicine at TUSM.
"We have known that GRK2 is involved in the pathological development of certain heart diseases, such as chronic heart failure, and that its increased activity can lead to the death of heart cells. But its mechanism for the latter was unclear," Koch said.
In addition, while the enzyme was known to be present in elevated levels in the hearts of patients with heart failure, the reasons for its rise were not fully understood.
Normally, GRK2 hangs out near the plasma membrane of heart cells, where it turns off certain signals transferred from the blood to the tissue.
But the researchers at Temple found that it moves to mitochondria in response to two classic features of heart disease, ischemic insult and ensuing oxidative stress.
These two processes, in which a momentary lapse in the delivery of oxygen-rich blood to diseased tissues causes a sudden increase in damaging reactive molecules, converge to stimulate the self-destruct program of heart cells.
They ultimately cause whole sections of heart tissue to die, leaving behind scars that can severely compromise the ability of the heart to function properly.
Koch's team found that in ischemic heart cells the movement of GRK2 from the cell membrane to mitochondria is chaperoned by a substance called heat-shock protein 90 (Hsp90), which is produced in cells in response to stress.
By blocking Hsp90's ability to bind to GRK2, the researchers were able to prevent the enzyme's delivery to mitochondria.
The results are published in the journal Circulation Research.
Source: ANI
