NCO-700 is a newly synthesized inhibitor of both
cathepsin B and
calcium-activated neutral protease. We examined whether
NCO-700 inhibits degradation of myofibrillar
proteins induced by cardiac
ischemia in dogs anesthetized with
pentobarbital. Cardiac
ischemia was produced by complete occlusion of the left anterior descending coronary artery (LAD) for 3 or 6 hr. Myofibrils were prepared from the ischemic myocardium, in which LAD was occluded, and from the nonischemic myocardium, in which LAD was not occluded. Electrophoresis of myofibrils prepared from the ischemic myocardium revealed that there were many degradation bands of myofibrillar
proteins as well as the bands corresponding to
alpha-actinin (AN), the 55 kDa
protein (55 K), actin (A),
tropomyosin (TM),
troponin I (TN I),
myosin light chain 1 (LC1) and
myosin light chain 2 (LC2). In addition, the content of AN, 55 K, A, TM, TN I, LC1 and LC2 in the ischemic myofibrils was lower than that in the nonischemic myofibrils. Treatment with
NCO-700 at the total dose of 20 mg/kg, which was injected intravenously before and during
ischemia, inhibited both appearance of the degradation bands and the decrease in the content of A, TM, TN I, LC1 and LC2 being produced by cardiac
ischemia.
NCO-700, however, did not inhibit the decrease in the content of 55K and AN being induced by
ischemia.