Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Inhibition with NCO-700, a protease inhibitor, of degradation of cardiac myofibrillar proteins during ischemia in dogs. 406 61

Overactivation of calcium-activated neutral protease (calpain) has been implicated in the pathophysiology of several degenerative conditions, including stroke, myocardial ischemia, neuromuscular degeneration, and cataract formation. Alpha-mercaptoacrylate derivatives (exemplified by PD150606), with potent and selective inhibitory actions against calpain, have been identified. PD150606 exhibits the following characteristics: (i) Ki values for mu- and m-calpains of 0.21 microM and 0.37 microM, respectively, (ii) high specificity for calpains relative to other proteases, (iii) uncompetitive inhibition with respect to substrate, and (iv) it does not shield calpain against inactivation by the active-site inhibitor trans-(epoxysuccinyl)-L-leucyl-amido-3-methylbutane, suggesting a nonactive site action for PD150606. The recombinant calcium-binding domain from each of the large or small subunits of mu-calpain was found to interact with PD150606. In low micromolar range, PD15O6O6 inhibited calpain activity in two intact cell systems. The neuroprotective effects of this class of compound were also demonstrated by the ability of PD150606 to attenuate hypoxic/hypoglycemic injury to cerebrocortical neurons in culture and excitotoxic injury to Purkinje cells in cerebellar slices.
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PMID:An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. 869 79