alpha-chymotrypsin and Heart-Diseases

Recent reports demonstrate that multiple forms of cardiovascular stress, including pressure overload, chronic ischemia, and infarction-reperfusion injury, provoke an increase in autophagic activity in cardiomyocytes. However, nothing is known regarding molecular events that stimulate autophagic activity in stressed myocardium. Because autophagy is a highly conserved process through which damaged proteins and organelles can be degraded, we hypothesized that stress-induced protein aggregation is a proximal trigger of cardiomyocyte autophagy.. Here, we report that pressure overload promotes accumulation of ubiquitinated protein aggregates in the left ventricle, development of aggresome-like structures, and a corresponding induction of autophagy. To test for causal links, we induced protein accumulation in cultured cardiomyocytes by inhibiting proteasome activity, finding that aggregation of polyubiquitinated proteins was sufficient to induce cardiomyocyte autophagy. Furthermore, attenuation of autophagic activity dramatically enhanced both aggresome size and abundance, consistent with a role for autophagic activity in protein aggregate clearance.. We conclude that protein aggregation is a proximal trigger of cardiomyocyte autophagy and that autophagic activity functions to attenuate aggregate/aggresome formation in heart. Findings reported here are the first to demonstrate that protein aggregation occurs in response to hemodynamic stress, situating pressure-overload heart disease in the category of proteinopathies.

Topics: Animals; Animals, Newborn; Autophagy; Cells, Cultured; Chymotrypsin; Genes, Reporter; Heart Diseases; Heart Failure; Heart Ventricles; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Pressure; Proteins; Rats; Rats, Sprague-Dawley; Transfection; Ubiquitin; Ventricular Function

Proteinase-inhibitor balance in human plasma before and after artificial blood circulation was examined. It was shown that trypsinlike and chemotrypsinlike proteinases activities after this procedure were 1.6 and 2.8 times higher and antitryptic activity 1.2 times lower than in the same patients before the procedure. The 40-50% decrease of proteinase activity in human plasma after artificial blood circulation was observed as a result of in vitro plasmasorption on immobilized human urinary trypsin inhibitor.

Topics: Adult; Chymotrypsin; Enzyme Activation; Extracorporeal Circulation; Female; Glycoproteins; Heart Diseases; Humans; In Vitro Techniques; Male; Middle Aged; Pancreatic Elastase; Postoperative Period; Trypsin

Topics: Acute Disease; Adult; Aged; Amylases; Arrhythmias, Cardiac; Chymotrypsin; Coronary Disease; Electrocardiography; Female; Heart Conduction System; Heart Diseases; Humans; Male; Middle Aged; Pancreatitis; Transaminases; Trypsin; Vasomotor System; Water-Electrolyte Balance

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Arrhythmias, Cardiac; Atrial Fibrillation; Chymotrypsin; Coronary Disease; Dogs; Drug Hypersensitivity; Electrocardiography; Esterases; Fibrinolysin; Heart Conduction System; Heart Diseases; Horses; Humans; Immune Sera; Immunoglobulin G; Injections, Intravenous; Papain; Penicillins; Peptide Hydrolases; Rabbits; Stimulation, Chemical; Trypsin; Tuberculin

Topics: Adrenocorticotropic Hormone; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitussive Agents; Atropine; Balneology; Bronchitis; Bronchitis, Chronic; Chymotrypsin; Climate; Cortisone; Cysteine; Dyspnea; Ephedrine; Exercise Therapy; Heart Diseases; Humans; Hydrocortisone; Hypnotics and Sedatives; Theophylline; Trypsin; Vaccination

Topics: Chymotrypsin; Enzyme Inhibitors; Heart; Heart Diseases; Hematologic Diseases; Humans; Serum

Topics: Chymotrypsin; Enzyme Inhibitors; Heart; Heart Diseases; Hematologic Diseases; Humans