DYSTROPHIN PROTEOLYSIS: A POTENTIAL TARGET FOR MMP-2 AND ITS PREVENTION BY ISCHEMIC PRECONDITIONING

BUCHHOLZ B; PÉREZ V; SIACHOQUE NA; MIKSZTOWICZ V; BERG G; RODRIGUEZ M; DONATO M; GELPI RJ

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2014 vol. 307 p. 88 - 96

0363-6135

Dystrophin is responsible for the mechanical stabilization of the sarcolemma and it has been shown that it is one of the most sensitive proteins to ischemic injury. However, the enzyme responsible for this proteolysis is still unknown. Isolated rabbit hearts were subjected to 30 minutes of global ischemia with and without reperfusion (180 minutes) to determine whether dystrophin is cleaved by MMP-2 during acute ischemia, and whether ischemic preconditioning (Pc) prevents dystrophin breakdown through MMP-2 inhibition. The activity of MMP-2 was evaluated by zymography and using doxycycline as an inhibitor. Also, to stimulate MMP-2 activity without ischemia, SIN-1 was administered in presence and in absence of doxycycline. Finally, we considered the Pc effect on the MMP-2 activity and the dystrophin expression. Dystrophin level decreased during ischemia, reaching 21% of control values (p