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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considering the important role of the phosphocreatine energy shuttle in contractile function of the heart we decided to study the different components of this shuttle in STZ-induced diabetic rat heart with a known diabetic related cardiomyopathy. Diabetes produced a gradual decline in total CK activity, reaching a maximum of 35-40% decrease after 4 weeks of diabetes, in both atria and ventricles. All of the CK isoenzymes including the mitochondrial CK (CKm) were reduced but to a different extent in these two tissues. The percentage reduction in diabetic ventricles was BB greater than MB greater than CKm greater than MM and in atria was CKm greater than BB greater than MB greater than MM. A major difference between atrium and ventricle was the greater loss of CKm in diabetic atria than diabetic ventricle (75% in atria vs 32% in ventricle). The B subunit seemed to be the one that was affected the most followed by CKm isoenzyme and then the M subunit. The bound myofibrillar CK isoenzyme, expressed as units of activity/mg of myofibrillar protein, was not affected by 4 weeks of diabetes. The high energy phosphates were also reduced in diabetic heart with a greater reduction in phosphocreatine (43-45%) and a smaller change in ATP (27%). Mitochondrial oxidative phosphorylation with alpha-ketoglutarate was reduced (55%) in diabetic heart, whereas, there was no difference when succinate was used as substrate. These changes were reversible by 4 weeks of insulin treatment. The loss of CKm, phosphocreatine and the reduction in mitochondrial oxidative phosphorylation, could result in an inefficient phosphocreatine energy shuttle which could contribute to the cardiac functional defects associated with diabetes.
J Mol Cell Cardiol 1991 Nov
PMID:Alteration of the phosphocreatine energy shuttle components in diabetic rat heart. 180 23

A novel, simple, rapid and reproducible microassay is used for kinetic analysis of Ca-sequestration by homogenates of myocardium of turkeys with furazolidone-induced congestive cardiomyopathy. The assay monitors Ca in real-time using dual-emission ratiometric spectrofluorometry and the Ca-indicator dye indo-1. Using this assay and isolated SR studies we make several novel findings regarding the mechanism of SR failure in furazolidone cardiomyopathy. Qualitative differences in Ca-sequestration were not detected between groups. However, compared to controls the furazolidone treatment resulted in: 1) 50% depression in maximal activities (1.54 +/- 0.36 vs 0.73 +/- 0.12 microM/sec); 2) 2-fold increases in post-sequestration concentrations of ionized Ca (79 +/- 23 vs 141 +/- 13 nmol Ca/L homogenate); 3) 2-fold increases in Ca half-life (415 vs 790 msec); and 4) 25% increased passive Ca-binding capacity of homogenates. The Ca-ATPase specific activity of isolated sarcoplasmic reticulum was 60% increased in congestive cardiomyopathy (543 +/- 140 vs 873 +/- 108 nmol ATP hydrolyzed/min/mg membrane protein) although membrane yield was 20% decreased (0.79 +/- 0.09 vs 0.63 +/- 0.03 mg/g heart). The increased ATPase and decreased Ca-uptake activities in combination with the occurrence of 36% cardiac hypertrophy and 19% decreased body weights resulted in estimates of the relative energy cost to the animal for myocardial Ca transport being 5.5-fold increased with cardiomyopathy (20.5 vs 111 nmol ATP hydrolyzed per microM decrease of sarcoplasmic free Ca/kg body weight). These data indicate that congestive cardiomyopathy is associated with markedly increased permeability of sarcoplasmic reticulum to Ca and compensatorily increased Ca-ATPase activity. Accelerated energy consumption due to the increased energy cost of Ca transport and increased time of myocyte activation are predicted to predispose the myocardium to fatigue and irreversible failure.
Mol Cell Biochem 1991 Mar 27
PMID:Myocardial Ca-sequestration failure and compensatory increase in Ca-ATPase with congestive cardiomyopathy: kinetic characterization by a homogenate microassay using real-time ratiometric indo-1 spectrofluorometry. 182 61

The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6-hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat.
Exp Mol Pathol 1991 Feb
PMID:Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat. 189 32

1,2-Diacylglycerol is believed to play an important role in cellular functions through protein kinase C activation, although its role in cardiac functions remains largely unexplored. We determined the level of 1,2-diacylglycerol and its fatty acid composition in heart tissues from Syrian hamsters with hereditary cardiomyopathy (BIO 14.6 strain) during the development of congestive heart failure from 90 days to 240 days of age. The myopathic hamsters had lower contents of triglyceride and of the major phospholipids, phosphatidylcholine, phosphatidylethanolamine and cardiolipin, in the myocardium when compared to normal hamsters, whereas there was no difference in the cholesterol content. No difference in the myocardial 1,2-diacylglycerol content was observed at 90 days of age. On the other hand, 1,2-diacylglycerol contents in myopathic hearts at 160 and 240 days of age were significantly lower by 21% and 52%, respectively, then in age-matched normal hamsters. The oldest hamsters (240-day-old) showed reduced 1,2-diacylglycerol levels in both groups despite an age-related increase in most lipids. The 1,2-diacylglycerol fatty acid composition profile was found to be different from that of other lipids, and there were several differences in the fatty acid composition of 1,2-diacylglycerol between the two groups at 240 days of age. These results indicate that decreased levels of 1,2-diacylglycerol occur concomitantly with congestive heart failure in the myopathic hamsters.
J Mol Cell Cardiol 1991 Apr
PMID:Decreased 1,2-diacylglycerol levels in myopathic hamster hearts during the development of heart failure. 194 78

The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of patients.
J Mol Cell Cardiol 1990 Oct
PMID:Enhanced deposition of predominantly type I collagen in myocardial disease. 209 38

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca2(+)-dependent Mg-ATPase and myosin Ca2(+)- and K+EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca2(+)-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca2+ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca2(+)-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.
Mol Cell Biochem 1990 Jul 17
PMID:Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure. 214 90

The characteristics of high affinity dihydropyridine binding sites were compared in normal and cardiomyopathic hamster hearts to probe for possible defects in the calcium channel which could lead to calcium overload and, in turn, to the muscle necrosis characteristic of cardiomyopathy. Kinetic studies of the temperature dependence of [3H]-nitrendipine binding to ventricular homogenates from 60-day-old normal and cardiomyopathic hamsters showed that, in normal hamsters, the rate of dissociation (0.049 +/- 0.006/min at 25 degrees C) was highly temperature-dependent (Q10 = 4.40 +/- 0.69) and that neither the rate nor the temperature dependence was influenced by disease. The rate of association (1.12 +/- 0.11/min/nM at 25 degrees C) was weakly temperature-dependent (Q10 = 1.25 +/- 0.04) and similarly unaffected by disease. The rate of dissociation of [3H]-nitrendipine was increased by verapamil and decreased by diltiazem with little effect on the association rate. Allosteric interactions of diltiazem and verapamil with the dihydropyridine receptor were identical in normal and cardiomyopathic hearts and, together with the normal temperature sensitivity, show that there is no abnormality at the related binding sites for nitrendipine, verapamil and diltiazem in the calcium channel of the cardiomyopathic heart.
J Mol Cell Cardiol 1990 Sep
PMID:[3H]-nitrendipine binding in normal and cardiomyopathic hamster hearts: modulation by temperature, verapamil and diltiazem. 217 94

The aim of this study was to determine whether variations of isomyosin expression occurred during doxorubicin-induced cardiomyopathy. A suitable experimental model in which pure delayed cardiotoxic effects could be easily studied was adopted. Young adult female Sprague Dawley rats received 9 mg/kg of doxorubicin (DXR) i.v. divided into three subdoses of 3 mg/kg every third day. Control animals received equal volumes of saline. The animals were examined 9 weeks after treatment. At this time the animals treated with DXR showed ECG alterations, reduction of body weight and a marked decrease of both atrial and ventricular mass, but were still fully hemodynamically compensated. Loss of myofibrillar material could be documented by the reduced recovery of myofibril and myosin. The contractile response of papillary muscles isolated from the right ventricle of treated animals was markedly impaired. Ca-Mg-activated and Mg-activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were determined on ventricular myocardium of control and treated animals. Both myofibrillar and myosin ATPase activities were found to be significantly reduced. Pyrophosphate gel electrophoresis of purified myosin was carried out. The isomyosin pattern of DXR-treated animals showed a pronounced shift towards V3, the percent of alpha heavy chains being 54.6% in treated rats (80.5% in control rats). This isomyosin shift can explain the reduced myofibrillar and myosin ATPase activity found in treated animals.
J Mol Cell Cardiol 1989 Jan
PMID:Reduction of myofibrillar ATPase activity and isomyosin shift in delayed doxorubicin cardiotoxicity. 252 75

Human picornaviruses include rhinoviruses and enteroviruses which are responsible for both common and severe clinical diseases. Rhinoviruses are a frequent cause of respiratory infections while members of enterovirus subgroups, polio, coxsackie and ECHO viruses are often responsible for infections of the central nervous system, myocarditis, myositis etc. Human picornaviruses consist of nearly two hundred serotypes and therefore their specific identification after virus isolation, or the diagnosis based on the detection of immune response in patients, is problematic and does not usually provide virological diagnosis at the acute phase of illness. New methods for detection of picornavirus genomic RNA together with increasing knowledge of the nucleotide sequences of this virus group offer interesting possibilities for diagnostic procedures. Spot hybridization, in situ hybridization and enzymatic amplification of specific sequences have successfully been used for this purpose. Probes covering the 5' non-coding part of the genome, and also sequences derived from the region coding for non-structural proteins, can be used as broadly reacting reagents in picornavirus detection. Specific sequences are mainly found in the capsid protein region of the genome. cDNA probes and synthetic oligonucleotides are useful in rapid identification of picornaviruses after amplification in cell cultures and in epidemiological analysis. The biochemical amplification methods may enable recognition of picornaviruses directly in clinical samples in the near future. In situ hybridization methods have been of special interest because they can be used to reveal the presence of enterovirus genomes in biopsy specimens from e.g. affected heart muscle in patients with myocarditis and cardiomyopathy.
Mol Cell Probes 1989 Dec
PMID:Identification of human picornaviruses by nucleic acid probes. 255 19

To determine whether the electrical changes associated with cardiac hypertrophy are due to alterations in the membrane properties of individual hypertrophied cells, we recorded action potentials in single myocytes isolated from normal and hypertrophied hearts. Cardiac hypertrophy was produced by a gradual pressure overload created by placing a band around the ascending aorta in young guinea-pigs (200-250 g). Almost half the animals that developed left ventricular (LHV) hypertrophy also developed evidence of cardiac dysfunction. Action potentials were recorded with standard microelectrodes in single ventricular myocytes isolated by enzymatic dispersion of the heart. The action potential duration at 1 Hz was significantly longer in hypertrophied cells than in control cells. The degree of action potential prolongation in isolated cells did not correlate with the degree of hypertrophy but did correlate with the degree of myocardial disease, the duration being longer in hypertrophied myocytes from dyspneic than in those from non-dyspneic animals. The resting potential was significantly lower in hypertrophied myocytes from dyspneic animals than in hypertrophied cells from non-dyspneic animals or control cells stimulated at 5 Hz. The relationship between the frequency of stimulation (0.33, 1, and 5 Hz) and action potential duration was steeper in hypertrophied than normal myocytes. The mean membrane capacitance (cm) of hypertrophied myocytes increased by 31% over the control value. Thus, isolated hypertrophied myocytes retain the prolonged duration of the action potential and the exaggerated dependence of duration on rate observed in intact hypertrophied muscle. The increased duration of the action potential in hypertrophied cells cannot be readily attributed to the observed increase in cm. Our results indicate that the membrane changes responsible for the altered electrical properties of hypertrophied myocardium are due to an effect of hypertrophy on individual myocytes and that the prolonged duration of the action potential is probably due to changes in active currents flowing during repolarization.
J Mol Cell Cardiol 1989 Jul
PMID:Electrophysiologic characteristics of single myocytes isolated from hypertrophied guinea-pig hearts. 279 65


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