Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The expression of various proto-oncogenes was evaluated in the Syrian hamster with hereditary idiopathic cardiomyopathy. mRNA from the heart and aorta of controls (BIO-RB) and cardiomyopathic hamsters (UM-X7.1 strain, BIO 14.6 line) was tested using RNA hybridization techniques. Of the 19 different v-oncogene probes used in the study, only the v-myc probe revealed a substantially greater expression of oncogene in the 30th day of cardiomyopathic hamster heart than in control hamster heart. The amplified expression of c-myc was also observed in the heart of 1-year-old, but not of 7-day-old cardiomyopathic hamster. Overexpression of c-myc, otherwise associated with the regulation of cell differentiation or rapid growth, may relate to the pathological state or pathogenesis of the hereditary cardiomyopathy.
J Mol Cell Cardiol 1988 Sep
PMID:Cellular oncogene expression in the idiopathic cardiomyopathic hamster heart during the growing process. 323 May 85

Free radicals have been suggested to play a role in adriamycin-induced cardiomyopathy. Adriamycin-induced myocardial effects were examined in rats maintained on a vitamin E deficient diet. Animals were divided into four groups: I, control; II, adriamycin-treated; III, vitamin E deficient diet; IV, vitamin E deficient diet plus adriamycin treatment. Adriamycin-treated animals (groups II and IV) were given six injections (i.p.) over two weeks for producing a cumulative dose of 15 mg/kg. Animals in groups III and IV were placed on vitamin E deficient diet starting two weeks prior to the first injection of adriamycin or vehicle. Myocardial tissue analysis were performed on animals sacrificed 1 week after the last injection. Mortality was significantly higher in group IV which also showed doubling of myocardial malondialdehyde content relative to the non-adriamycin-treated vitamin E deficient group (III). Myocardial cell damage in group IV was characterized by separation of the external lamina, subsarcolemmal changes, mitochondrial swelling and myofibril dropout. Group II hearts showed only a mild dilation of the sarcotubules and swelling of the mitochondria. Total sialic acid content of the sarcolemma in groups II, III and IV was 55, 90 and 24% of the control values in group I. These data show a characteristic sarcolemmal injury produced by adriamycin in hearts of animals with reduced antioxidant capacity which is probably mediated by increased free radical activity as well as lipid peroxidation.
Mol Cell Biochem 1988 Dec
PMID:Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes. 323 Dec 21

Functional states of cardiac contractile apparatus and mitochondria were studied in hereditary cardiomyopathic hamsters (CHF 146) and control golden hamsters using cardiac fibers skinned by two different techniques. The Triton X-100 skinned fibers obtained from diseased animals of 175 to 200 days old, or from control animals, demonstrated the same resting and maximal Ca-activated tensions, the same stiffness, the same rate of tension recovery after quick stretch; the fibers from cardiomyopathic animals differed only by a slightly increased calcium sensitivity. Functional activity of myofibrillar creatine kinase in cardiomyopathy was decreased as indicated by a smaller shift in the pMgATP/rigor tension curve to lower [MgATP] in the presence of phosphocreatine and by a slower rate of the tension recovery after quick stretch in the presence of phosphocreatine and ADP (without ATP). The saponin-skinned fibers allow evaluation of the respiration properties of the total tissue mitochondria. Data obtained in the preparations isolated from diseased animals of two ages (75 to 100 and 175 to 200 days) showed that the ratio of maximal ADP-stimulated respiration rate to the respiration rate in the absence of ADP (an analog of respiration control index) was unchanged in myopathy as compared with age-matched controls. However stimulation of respiration after an addition of creatine at submaximal ADP concentration was observed to be respectively 1.45 times and 3.5 times less in the preparations from younger and older myopathic animals as compared with their respective controls, thus indicating the impairment of functional coupling between mitochondrial creatine kinase reaction and oxidative phosphorylation. These results suggest that hereditary cardiomyopathy is associated with alterations in myocardial creatine kinase system, while myofilaments and mitochondria preserve their basic functional properties.
J Mol Cell Cardiol 1988 Apr
PMID:Functional state of myofibrils, mitochondria and bound creatine kinase in skinned ventricular fibers of cardiomyopathic hamsters. 326 69

Doxorubicin (Adriamycin, ADR) is an anthracycline antineoplastic with the serious side effect of dose-related cardiomyopathy. A model of ADR cardiotoxicity was created to examine some subcellular toxic effects of ADR with cultured cardiac myocytes (CMCs) exposed to 1 x 10(-7) to 1 x 10(-5) M ADR for 24 to 48 hr. Lactate dehydrogenase (LDH) activity was monitored in the CMC medium to monitor CMC damage as a function of ADR concentration. A four- to eightfold elevation of LDH activity in medium of CMCs exposed to 1 x 10(-6) to 1 x 10(-5) M ADR was found. No change in LDH activity was detected in medium of CMCs exposed to 1 x 10(-7) M ADR or in control CMCs after 24 or 48 h ADR exposure. Data suggest a dose-dependent effect of ADR on LDH activity in CMC medium. Serial monitoring of LDH in media of ADR-exposed CMCs may correlate with other evidence of ADR cardiotoxicity in vitro.
Exp Mol Pathol 1988 Jun
PMID:Lactate dehydrogenase activity in cultured neonatal rat heart cells exposed to doxorubicin. 337 55

The effects of a sudden decrease in coronary perfusion pressure from 140 to 0 cmH2O for a 10-second interval were analyzed in normal and cardiomyopathic hamster hearts to determine whether cardiomyopathy would affect the relationship between altered coronary perfusion pressure and left ventricular geometry, wall thickness, myocardial hydrodynamics, and hemodynamics. In normal hamsters, an acute reduction in coronary perfusion pressure resulted in a decrease in left ventricular short axis epicardial cross-sectional area, base to apex length, diastolic wall thickness, myocardial water content and developed pressure. In cardiomyopathic hamsters all results induced by lowering the hydrostatic pressure of the perfusing medium were the same except that diastolic wall thickness failed to decline, indicating a decrease in intramyocardial elasticity in dilated cardiomyopathy. In parallel studies, hearts were freeze clamped at end-diastole and high energy phosphates and energy metabolites analyzed. In both normal and cardiomyopathic hamsters no significant changes were observed in ATP, PCr, or Pi levels at 10 s following the decrease in perfusion pressure. However, during the abrupt decrease in coronary perfusion pressure adenosine increased and cAMP decreased in both groups of animals. The erectile effect of altered coronary perfusion pressure is partially attenuated in the cardiomyopathic hamster in which no change in diastolic wall thickness occurs during an abrupt change in the hydrodynamics of the heart.
J Mol Cell Cardiol 1987 Oct
PMID:Effects of altered coronary perfusion pressure on function and metabolism of normal and cardiomyopathic hamster hearts. 343 52

Recent experiments from our laboratory have shown that the ultrastructure and protein composition of gap junctions isolated from rat ventricles are tissue specific, i.e., markedly different from gap junctions of liver and lens. The differences include a cytoplasmic surface component characteristic for cardiac gap junctions; this component can be visualized by two ultrastructural techniques: as a fuzzy layer in electron micrographs of thin-sectioned junctional pellets and as cytoplasmic surface particles in deep-etched freeze-fractured junctions. The component corresponds to a Mr 17,500 cytoplasmic surface domain of each of the six (Mr 47,000) rat heart gap junctional channel protein subunits that make up the gap junctional channel hexamer known as a connexon. The cytoplasmic surface component is localized at the carboxy-terminal of the subunit. Within the cytoplasmic surface component, rat cardiac gap junctions are cross-linked by disulfide linkages between subunits of the same connexon and between subunits of adjacent connexons. By contrast, the Mr 28,000 liver gap junctional subunit lacks a comparably large cytoplasmic surface component, cytoplasmic surface fuzz, cytoplasmic surface particles, and intra- and interconnexon disulfide linkages. Most of these unique characteristics of cardiac gap junctions were discovered in junctions isolated from rat ventricles. Unlike liver and lens gap junctions, cardiac gap junctions from humans, non-human primates, or other large mammals have not previously been isolated and characterized. Here we report the isolation of unproteolyzed gap junctions from the ventricle of a 24 year-old man with advanced cardiomyopathy whose heart was removed for replacement by a transplanted heart.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Feb
PMID:Human cardiac gap junctions: isolation, ultrastructure, and protein composition. 357 42

Phosphatidylethanolamine (PE) N-methylation activity was studied in rat heart sarcolemma at 1, 3, 9 and 24 h after an intraperitoneal injection of isoproterenol (40 mg/kg). Three reaction sites for PE N-methylation were examined by assaying the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (AdoMet) into sarcolemmal PE molecules under optimal conditions. Total methylation activity at catalytic site I (studied by employing 0.055 microM AdoMet) was increased at 1 and 3 h after the isoproterenol injection and depressed at 24 h; 9 h samples showed no change. Similar biphasic alterations were seen for phosphatidyl-N-monomethylethanolamine, the major methylated product formed at site I. Alterations in the methylation activity at site I were associated with changes in Vmax values but the apparent affinity for AdoMet remained unaltered. No alterations were found in total methylation activities at sites II and III in isoproterenol treated preparations when studied by employing 10 and 150 microM AdoMet, respectively. An increase and a decrease in the PE N-methylation activity at site I were also observed in the sarcoplasmic reticular (microsomal) fraction from experimental hearts after 1 h and 24 h of the isoproterenol injection respectively, without changes at sites II and III. On the other hand, no changes were seen in the mitochondrial fraction. These results indicate biphasic alterations in the sarcolemmal and microsomal PE N-methylation activities during the development of catecholamine-induced cardiomyopathy.
J Mol Cell Cardiol 1987 Apr
PMID:Biphasic changes in the sarcolemmal phosphatidylethanolamine N-methylation activity in catecholamine-induced cardiomyopathy. 361 19

The isometric twitch properties of papillary muscles from hearts of 30- to 53-day-old cardiomyopathic hamsters (BIO 14.6) were studied before and after exposure to the cardiac glycoside, ouabain. The diseased tissue was weakly responsive to ouabain (3 to 100 microM), as compared to a more appreciable positive inotropic response in papillary muscle of similarly aged normal hamsters (BIO F1B). These data suggest that the activity of Na+,K+-ATPase is attenuated in the diseased sarcolemma. Pretreatment with the beta-adrenoceptor agonist, isoproterenol (0.1 microM), slightly increased the sensitivity of normal muscle to ouabain, however the response of myopathic muscle was greatly enhanced. These findings may be of significance to the genesis of cellular calcium overload hypothesized to be involved in the necrosis and degeneration of heart cells in this animal model of genetic cardiomyopathy.
J Mol Cell Cardiol 1987 Jun
PMID:The effect of ouabain on hearts of cardiomyopathic hamsters: potentiation by isoproterenol. 362 90

Rats were injected intraperitoneally with isoproterenol in dosage of 40 mg/kg body weight and heart microsomal and mitochondrial fractions were isolated 3, 9 and 24 h later. The heart/body weight ratio increased at 9 and 24 h after injection without any changes in the yield of subcellular organelles. Microsomal calcium uptake was significantly elevated at 3 h but returned to normal at 9 h and then became depressed 24 h post-injection. Mitochondrial calcium uptake was significantly increased 9 and 24 h after isoproterenol administration. Kinetic parameters of the calcium transport function indicated that the apparent affinity for Ca2+ remained unchanged, whereas Vmax values were altered in the experimental groups. Although there was no significant change in the phospholipid composition, the total phospholipid contents were increased (at 3, 9 and 24 h for microsomes; 3 and 9 h for mitochondria) in both types of organelles. The protein composition, as determined by gel electrophoresis, was altered in microsomes, but not in mitochondria. These results demonstrate rapid structural and functional changes in subcellular organelles. Such alterations may play an adaptive role in maintaining the intracellular calcium homeostasis during the development of catecholamine-induced cardiomyopathy.
J Mol Cell Cardiol 1985 Apr
PMID:Adaptive changes in subcellular calcium transport during catecholamine-induced cardiomyopathy. 402 Aug 77

The effect of therapeutic doses of digitalis in modifying neural activity has been the subject of considerable controversy. In earlier studies we reported an increase both in serotonergic activity in the posterior hypothalamus and pons-medulla and in cardiac sympathetic tone in the failing cardiomyopathic hamster. In this study we examine the effects of doses of digitoxin, known to be therapeutic for hamster heart failure, on monoamine neurotransmitter metabolism in the brain and heart during the cardiomyopathy. Both digitoxin and ASI-222, a polar amino-glycoside which does not cross the blood-brain barrier, given either acutely (6 mg/kg ip) or chronically (2 mg/kg/day ip for 10 days), normalized the failure-induced increase in serotonin turnover in the pons-medulla but had no effect on the changes in the posterior hypothalamus. Digitoxin therapy also reduced cardiac and adrenal sympathetic activity partially restoring cardiac catecholamine stores. In order to more clearly define the pathways involved we measured serotonin (microgram/g protein) in 18 brain nuclei after 10 days of digitoxin or vehicle treatment. Heart failure was associated with an increase in serotonin in five nuclei: the mammillary; bodies, ventromedial, periventricular and paraventricular nuclei of the hypothalamus, and the centralis superior nucleus of the raphe. Digitoxin therapy completely normalized the changes in the centralis superior and ventromedialis nuclei; neither congestive heart failure nor digitoxin affected serotonin levels in other nuclei. We conclude that there is an increase in activity in specific brain serotonergic nuclei in congestive heart failure. Digitalis reduces cardiac sympathetic tone and restores the changes in two of these nuclei: the ventromedial and the centralis superior.+2
J Mol Cell Cardiol 1985 Nov
PMID:Digitoxin therapy partially restores cardiac catecholamine and brain serotonin metabolism in congestive heart failure. 407 5


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