THE LYSOSOMAL ENZYMES ACTIVITY MODULATION BY MEANS OF DRUGJournal: I.P. Pavlov Russian Medical Biological Herald (Vol.4, No. 12)
Publication Date: 2003-11-10
Principles of biochemical diagnosis of myocardial infarction and role of lysosomal enzymes in the development of degradation of membrane structures of cardiomiocytes exposed to oxigen deficiency conditions are discussed. General characteristics of lysosomal enzymes, approaches to drug modulation of lysosomal activity, and modern concepts of mechanisms of regulation of lysosomal activity are reviewed. Some drugs exerting differently oriented effects on the level of calcium ions in cardiomyocytes (Verapamil, Diltiazem, Digoxin, and Azaklorzin) were tested experimentally (in vivo) for the ability to modify activity of lysosomal enzymesunder conditions of oxigen deficiency (e.g., against the background of experimental hyperlipidemia). Enzimes with different location in lysosomal compartment (acid phosphatase, beta-galactosidase, and katepsin D) were assayed in these experiments. It is shown that calcium antagonists Verapamyl (10 mg/kg per os, 1 mg/kg parenteral) and Diltiazem (4 mg/kg per os) were capable of protecting the membrane-lysosomal apparatus of the myocardium against myocardial ischemia. Protective effect was observed after single intake of these drugs (6 h before total acute ischemia of myocardium) and included limitation of myocardial acid hydrolase activity transition into nonprecipitated fraction and decrease in the activity of these enzymes in blood. A hypothesis of possible mechanisms of activity modulation of the lysosomal-vacuolar apparatus enzymes by calcium-regulation drugs is put forward. The areas of practical application of the effect of reversible target-oriented regulation of activity of myocardial lysosomal enzymes are discussed.
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