Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.4.1 (myosin ATPase)
 1,140 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histochemical and ultrastructural effects of extracorporeal circulation and aortic cross-clamping during coronary heart surgery have been examined in drill biopsy samples of the left ventricle in 22 patients. The biopsies were obtained before and after bypass with a DeSoutter drill. Histochemical studies indicated definite differences between control and experimental biopsies, with increased succinic dehydrogenase, cytochrome oxidase, and LDH activity, while phosphorylase A and myosin ATPase activities declined. Furthermore, free phospholipid levels increased, as determined by the acid hematein reaction. Ultrastructural examination demonstrated loss of glycogen, intracellular swelling, and mitochondrial damage, which included loss of matrix density, loss of cristae, and eventual disruption in the postbypass biopsy. These results, which closely resemble the effects of ischemia and reperfusion observed in animal experiments, suggest that the initial insult is a change in membrane permeability regulation.
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PMID:Histochemical and structural changes in human myocardial cells after cardiopulmonary bypass. 16 88

The localization of creatine kinase M (CK-M) in both normal and acute ischemic canine myocardial cells was studied by immunoelectron microscopy using the anti-CK-M Fab'-horseradish peroxidase conjugate. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15, 60, or 180 minutes. In the normal myocardial cells, CK-M was localized mostly in the A-band and some in the Z-line, M-line, sarcolemmal membrane, and membrane of sarcoplasmic reticulum. Most CK-M in the A-band appeared to associate with thick fibers. This finding strongly suggests that the CK associated with thick fibers may be the enzyme to rephosphorylate ADP produced by myosin ATPase. In 15 minutes of myocardial ischemia, CK-M showed only minimal changes in its location, i.e., almost similar to normal, indicating that the CK in the A-band still has the ability to couple with myosin ATPase. However, in 60 and 180 minutes of ischemia, the A-band CK dissociated markedly from thick fibers, diffused to the I-band and leaked out to the intercellular spaces. These results suggest that the dissociation and disappearance of the A-band CK from thick fibers induced by progress of myocardial ischemia disrupt the myocardial energy transport system via CK reaction, and lead to the irreversible injury of myocardial cells.
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PMID:[Immunoelectron microscopic studies on the localization of creatine kinase M in normal and ischemic myocardial cells]. 240 81

The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 +/- 10% of nonischemic myocardium, p less than 0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 +/- 7% compared to that of nonischemic myofibrils (p less than 0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 microM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 microM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.
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PMID:Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium. 295 65

After prolonged ischemia followed by reperfusion of the isolated rat heart, irreversible heart failure is associated with creatine kinase leakage from the cells. The possible implications of MM creatine kinase leakage from myofibrillar compartments on the contractile properties of ventricular muscle have been studied in control versus ischemic hearts. Total creatine kinase activity decreased in ischemic cells while creatine kinase and ATPase activities were not modified in isolated myofibrils. The efficiency of creatine kinase and phosphocreatine in the relaxation of rigor tension in skinned ventricular preparations was not changed after ischemia. Furthermore, neither the pCa/tension relationship nor the rate of tension development following length changes were modified by ischemia. These results show that the contractile properties of myofilaments as well as the functional coupling between myosin ATPase and creatine kinase are preserved in ischemic hearts suffering irreversible contractile failure.
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PMID:Contractile properties and creatine kinase activity of myofilaments following ischemia and reperfusion of the rat heart. 343 83

We used a modification of Langendorff's isolated perfused nonworking rat-heart model to study the effects of diabetes, insulin-treated diabetes, and hyperinsulinemia on left ventricular pressure, force of ventricular contraction, and myocardial contracture, before, during, and after 20 min of complete normothermic global ischemia. Untreated diabetic rat hearts behaved the same as normal hearts, but insulin-treated diabetic hearts had more ischemic and postischemic contracture (p less than .01), and less return of left ventricular function. Chronic insulin treatment potentiated ischemic contracture in diabetic and nondiabetic rat hearts. These results support the hypotheses that insulin can increase Ca++ actin-myosin ATPase activity, and increase the affinity of myofibrillar receptors for calcium, which may lead to increased ischemic contracture. Insulin as a risk factor in myocardial ischemia, cardiothoracic surgery and cardiac resuscitation, and other pathogenetic factors of "stone heart" development, deserve further investigation.
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PMID:Insulin worsens ischemia-induced myocardial contracture in the isolated rat heart. 351 78

A modified isolated canine gracilis model of acute complete muscle ischemia was developed and then tested metabolically and histologically in 25 animals to assess its validity. In each dog, both gracili were isolated on their major vascular pedicles. One muscle underwent ischemia and reperfusion by placing and removing microvascular clips on the artery and vein. The other gracilis muscle was used as a control. Total muscle blood flow measurements, blood samples, and muscle biopsies were taken every other hour for up to 11 hr after preparation. The fiber-type profile of the gracilis was determined bilaterally using a myosin ATPase stain (n = 10). The results verified these hypotheses: after surgical preparation, the right and left muscles in the same dog are equivalent metabolically, after a 2-hr stabilization period, gracilis blood flow, oxygen and glucose uptake, lactate release, and tissue glycogen, lactate, phosphocreatine, and ATP levels remain within normal limits and unchanged for the next 9 hr, the surgical isolation of the gracilis muscle on a single vascular pedicle does not result in significant metabolic changes, in this model, a 2-hr ischemia is reversible, but a 7-hr ischemia results in irreversible ischemic injury. As well, fiber-type profile, muscle blood flow, and metabolic parameters can very significantly among animals supporting the necessity of a contralateral control. Therefore, this modified gracilis muscle model with its contralateral muscle as a control is suitable for acute skeletal muscle ischemia experiments of at least 9-hr duration.
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PMID:An isolated skeletal muscle model suitable for acute ischemia studies. 374 95

To clarify the changes in creatine kinase M localization along with the progress of myocardial ischemia, immunoelectron microscopic studies were performed using rabbit anti-canine creatine kinase M Fab'-horseradish peroxidase conjugate in 21 dogs. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15 (n = 5), 30 (n = 5), 60 (n = 5), or 180 (n = 4) minutes. Two dogs were used as normal controls. As we have already demonstrated, most creatine kinase M in normal myocardial cells was localized over the entire A band in association with the thick filament, suggesting that creatine kinase in this region (A-band creatine kinase) was the enzyme coupled with myosin ATPase. After 15 minutes of ischemia, creatine kinase M showed only minimal changes in its location, indicating that A-band creatine kinase still has the ability to couple with myosin ATPase (reversible injury). However, after 30 minutes of ischemia, A-band creatine kinase diffused markedly to the I band (transitional phase), and after 60 minutes of ischemia, it leaked out to extracellular spaces (irreversible injury). After 180 minutes of ischemia, most A-band creatine kinase disappeared from the myocardial cells (coagulation necrosis). These features of creatine kinase M localization seemed to reflect each stage of ischemic cell injury. We conclude that myocardial ischemia results in a dissociation of creatine kinase molecules from the thick filament, which leads the energy transport system to destruction.
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PMID:Changes in creatine kinase M localization in acute ischemic myocardial cells. Immunoelectron microscopic studies. 840 63

Reactive oxygen species (ROS) have been reported to alter cardiac myofibrillar function as well as myofibrillar enzymes such as myosin ATPase and creatine kinase (CK). To understand their precise mode and site of action in myofibrils, the effects of the xanthine/xanthine oxidase (X/XO) system or of hydrogen peroxide (H2O2) have been studied in the presence and in the absence of phosphocreatine (PCr) in Triton X-100-treated cardiac fibers. We found that xanthine oxidase (XO), with or without xanthine, induced a decrease in maximal Ca(2+)-activated tension. We attributed this effect to the high contaminating proteolytic activity in commercial XO preparations, since it could be prevented a protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), and it could be mimicked by trypsin. In further experiments, XO was pre-treated with 1 mmo1/L PMSF. Superoxide anion production by the X/XO system, characterized by electron paramagnetic resonance spin-trapping technique, was not altered by PMSF. A slight increase in maximal force was then observed either with X/XO (100 mumol/L per 30 mIU/mL) or H2O2. pMgATP-rigor tension relationships have been established in the presence and in the absence of PCr to separate the effects of ROS on myosin ATPase and myofibrillar-bound CK. In the absence of PCr, pMgATP50, the pMgATP necessary to induce half-maximal rigor tension, was reduced from 5.03 +/- 0.17 (n = 21) to 4.22 +/- 0.22 (n = 4) after 25 minutes of incubation in the presence one of 30 mIU/mL. XO and 100 mumol/L xanthine or to 4.04 +/- 0.1 (n = 11) after incubation in the presence of 2.5 mmol/L H2O2. The ROS effects were partially prevented or antagonized by 1 mmol/L dithiothreitol. No effect was observed on pMgATP50 when PCr was absent. pCa-tension relationships have been evaluated to assess the effects of ROS on active tension development. Incubations with H2O2 induced on increase in Ca2+ sensitivity and resting tension when MgATP was provided through myofibrillar CK (PCr and MgADP as substrates) but not when MgATP was added directly. These results suggest that myofibrillar CK was inhibited by ROS. Active stiffness and the time constant of tension changes after quick stretches applied to the fibers were dose-dependently increased by H2O2 only in the presence of PCr. In addition, myofibrillar CK but not myosin ATPase enzymatic activity was depressed after incubation with either ROS. These results suggest that ROS mainly alters CK in myofibrils, probably by the oxidation of its essential sulfhydryl groups. Such CK inactivation results in a decrease in the intramyofibrillar ATP-to-ADP ratio. The effects of ROS on cytosolic and bound CKs may take part in the overall process of myocardial stunning after cardiac ischemia and reperfusion.
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PMID:Creatine kinase is the main target of reactive oxygen species in cardiac myofibrils. 863 32

Various protocols for the isolation and cultivation of adult rat cardiomyocytes were compared, and the cytoprotective potential of the reversible myosin ATPase inhibitor butanedione monoxime (BDM) was evaluated based on cell yield, cell vitality, lactate dehydrogenase (LDH) and creatine kinase (CK) release, and the mRNA expression of atrial natriuretic peptide (ANP). Overall, a yield of 11.9 x 10(6)cells with >92% cell vitality was obtained when BDM was added to the isolation and cultivation buffers. In contrast, cell vitality ranged from 30% to 70% and cell yield was (4-10) x 10(6) when standard methods for the isolation of cardiomyocytes were used. Butanedione monoxime, at a 15 mM concentration, was cytoprotective during the isolation and cultivation of heart muscle cells, as judged by the morphological appearance (rod shape, lack of bleb formation, and other cytoskeleton defects) and the mRNA expression of the ANP gene. The activities of LDH and CK were also significantly reduced (p < 0.05%) when BDM was added to the isolation and cultivation buffer. The results obtained with BDM warrant further investigation into its cytoprotective potential during ischemia and damage to the cytoskeleton.
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PMID:Butanedione monoxime increases the viability and yield of adult cardiomyocytes in primary cultures. 1221 98

The effect of myosin ATPase inhibitor, 2,3-butanedione monoxime (BDM; used in the range of concentrations 1.25-10.0 mM), on recovery of functions of isolated rat heart subjected to normothermic (37 degrees C) total ischemia for 35 min has been investigated. BDM perfusion was performed at a flow rate of 4 ml/min during 5 min before ischemia (BDM-I) or before 25-min reperfusion (BDM-R). Control hearts were perfused with Krebs solution at the same flow rate. The highest functional recovery of heart and coronary vessels was observed during infusion of 2.5 mM BDM before ischemia. At the end of reperfusion ATP and phosphocreatine (PCr) content in hearts of this group was significantly higher whereas the level of lactate was two times lower than in control; total creatine content (sigmaCr) did not differ from the initial level. Similar but less pronounced changes in the improvement of aerobic metabolism and maintenance of sigmaCr after reperfusion were also observed in the case of infusion of 2.5 mM BDM before reperfusion. They were consistent with reduced recovery of functions of heart and coronary flow compared with these parameters observed in the BDM-I group. 2.5 mM BDM caused almost 2-fold decrease in release of cardiac lactate dehydrogenase into myocardial perfusate in the BDM-I and BDM-R groups (compared with control); this suggests lower damage of cell membranes. These results suggest that improvement of energy supply of postischemic cardiomyocytes may be a key factor determining cardioprotector effectiveness of short-term administration of BDM before ischemia.
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PMID:[The effect of myosin ATPase inhibition on metabolic and functional recovery of isolated rat heart after global ischemia]. 2000 Jan 23


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