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 positive inotropic effects of thyroid hormone in the heart, increased force and velocity of contraction have been mostly attributed to modulation of myosin ATPase isoenzymes (V1, V2 and V3), and sarcoplasmic reticulum Ca2+ pumping activity. In addition, we have suggested that the effects on ventricular contraction result from a thyroid hormone-induced increase in L-type Ca2+ current (ICa,L). Due to the central role of ICa,L in excitation-contraction coupling, we studied mechanisms whereby thyroid hormone augments this current. Since thyroid hormone modulates adenylate cyclase activity in various tissues, we tested the hypothesis that the hormone activates adenylate cyclase, leading to increased cyclic adenosine monophosphate (cAMP) levels, protein kinase A activation, Ca2+ channel phosphorylation and increased ICa,L. We therefore stimulated or inhibited different sites along the "adenylate cyclase cascade", and measured ICa,L and isometric twitch in ventricular myocytes and papillary muscles from euthyroid and hyperthyroid guinea pigs. Our major findings were as follows. In euthyroid myocytes, 0.1 microM isoproterenol (Iso) increased ICa,L (at VM = 0 mV) from -7.04 +/- 0.72 to -22.26 +/- 1.88 pA/pF, P < 0.05, while in hyperthyroid myocytes (ICa,L = -21.48 +/- 2.94 pA/pF), Iso was ineffective. In euthyroid myocytes, intracellular application of cAMP (50 microM) was as potent as Iso, but ineffective in hyperthyroid myocytes. In hyperthyroid myocytes, a protein kinase A inhibitor (2 microM) lowered ICa,L from -26.82 +/- 1.54 to -10.17 +/- 1.70 pApF (P < 0.05), but had no effect in euthyroid myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of hyperthyroidism-induced modulation of the L-type Ca2+ current in guinea pig ventricular myocytes. 133 56

Thyroid hormone-induced changes in cardiac function have been recognized for over 150 years; however, the biochemical basis of triiodothyronine (T3) action in the heart has been intensely investigated only during the last two decades. T3-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. The c-erb A protein is the cellular homologue of the viral erythroblastosis A (v-erb A) protein, which causes red cell leukemia in chickens. Currently, three T3-binding isoforms of the c-erb protein and two non-T3-binding nuclear proteins that exert positive and negative effects on T3-responsive cardiac genes have been identified. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, thyroid hormone leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart.
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PMID:Biochemical basis of thyroid hormone action in the heart. 218 6

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

The effects of amiodarone on heart weight, production of 14C-CO2 from labelled glucose, myosin ATPase activity, and myosin isoenzyme patterns were determined by comparing control and amiodarone-treated male Wistar rats. Since it has been suggested that amiodarone may interfere with thyroid hormone action on the heart, similar experiments were also carried out in hypothyroid and amiodarone-plus-triiodothyronine(T3)-treated rats, and the data were compared to those obtained in amiodarone-treated rats. Amiodarone treatment for 6 weeks resulted in lower heart weight, decreased atrial production of 14C-CO2 from labelled glucose, decreased myosin Ca-ATPase activity, and preferential synthesis of V3 isomyosin. These effects were similar to those observed in hypothyroid rats but were lesser in magnitude. T3 treatment of amiodarone-treated rats reversed all the changes induced by amiodarone. Serum thyroxine (T4) was higher in amiodarone-treated than in control rats, while serum T3 was similar. Serum T3 was higher in the amiodarone-plus-T3 than in the amiodarone-treated group. These results show that 1) amiodarone-induced changes resemble hypothyroidism with respect to cardiac myosin expression and atrial CO2 production, 2) amiodarone causes hypothyroid-like changes despite normal serum T3 and increased serum T4, and 3) T3 reverses the effects of amiodarone. These data support the hypothesis that amiodarone inhibits the action of thyroid hormone on the heart.
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PMID:Effect of amiodarone on rat heart myosin isoenzymes. 295 16

Young rats fed a protein-deficient diet have elevated total triiodothyronine (T3) levels in spite of decreased skeletal muscle protein turnover. Interpretation of the thyroid status of these animals is complicated by increased T3 binding by serum proteins. Free T3 levels ranging from normal to low and decreased resting oxygen consumption have been reported. To investigate the thyroid status of animals fed a protein-free diet, ventricular myosin ATPase activity and isomyosin profile have been used as an index of thyroid hormone activity. The effect of the protein-free diet has been compared to a restricted high protein-low carbohydrate diet, which causes clear evidence of decreased thyroid hormone effect. After 28 d, calcium-activated myosin ATPase activity was 1.50 +/- 0.05 mumol Pi/(mg protein.min) in animals fed the basal diet, 1.16 +/- 0.03 mumol Pi/(mg protein.min) in animals fed the restricted high protein-low carbohydrate diet and 1.48 +/- 0.04 mumol Pi/(mg protein.min) in animals fed the protein-free diet. In addition, a shift in isomyosin content with the appearance of V2 and V3 isomyosins occurred with the restricted high protein-low carbohydrate diet but not the protein-free diet. The failure of the protein-depleted rats to decrease myosin ATPase activity and alter isomyosin content suggests that they are euthyroid.
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PMID:Comparison of the effect of a protein-free and restricted high protein-low carbohydrate diet on ventricular myosin ATPase activity and isomyosin profile in young rats: evidence that protein-depleted animals are euthyroid. 296 54

To investigate the mechanism of thyroid hormone-induced cardiac hypertrophy, we have studied the in vivo changes in cardiac size and total myocardial content of both membrane and cytoskeletal enzymes in the rat after the administration of excess thyroid hormone. In response to 50 micrograms T4/day, there is a significant increase in heart rate and heart work associated with an increase in total heart size and protein content. Measurements of the specific activity of Na,K-ATPase and p-nitrophenol phosphatase demonstrate a small but significant increase in specific activity, while the specific activity of myosin ATPase is unchanged. To further probe the mechanism for T4-mediated hypertrophy we studied the in vivo effects of beta-adrenergic blockade on rat heart size. When animals were treated with both T4 and propranolol (10 mg/animal.day) cardiac hypertrophy was prevented. Propranolol alone at this dose did not affect heart rate, heart weight, or serum levels of T4 and T3. The present data suggest that 1) the hypertrophic response of the myocardium to excess thyroid hormone involves cytoplasmic as well as membrane proteins, 2) the increase in total myocardial protein, which can be blocked by propranolol, is indirectly mediated by increases in cardiac work rather than a direct effect of thyroid hormone.
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PMID:Thyroxine-induced cardiac hypertrophy: time course of development and inhibition by propranolol. 296 37

Studies were conducted to analyze the effect of the thyroid hormone on ventricular myosin during ontogenesis of mice, rats and rabbits. Hypothyroidism was induced in mice and rats by administering propylthiouracyl in drinking water. Rabbits were made hyperthyroid by chronic administration of thyroxine. The change in the thyroid state of rats and rabbits influenced young and adult animals differently depending on whether V1 or V3 was the major ventricular isomyosin form present. Measurements of Ca2+-ATPase activity of myosins from young and old control animals and from animals with changed thyroid state showed that hypothyroidism in rats is associated with a greater decrease of myosin ATPase in young rats which contain V1 isomyosin only, when compared with old rats which contain a preponderance of V3 isomyosin and less of the V1 form. In rabbits, ATPase activity of ventricular myosin was more elevated after thyroxine administration in adult rabbits, which contain V3 isomyosin only, than in young rabbits in which myosin consists of V1 and V3 isomyosins. Ventricular myosins of young and adult mice did not differ in their ATPase activity and the treatment of mice with propylthiouracyl had only slight effect on myosin ATPase. It can be concluded based on these results that the hypothesis concerning hypothyroidism inducing transformation of V1 into V3 isomyosin does not hold generally.
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PMID:Ventricular myosin from young and adult animals with respect to the thyroid state. 296 48

This study was designed to investigate the changes in cardiac contractile properties induced by triiodothyronine (T3) administration in adult rats. Myofibrils and myosin were isolated from ventricular muscles from euthyroid and hyperthyroid animals and enzymatically and electrophoretically characterized. The time course of the isometric response, the force velocity curve, the force interval relation were studied in papillary muscles isolated from the right ventricles of euthyroid and hyperthyroid rats. T3 administration induced significant increases in Mg2+ activated myofibrillar ATPase activity (+11.4%) and in Ca2+ activated myosin ATPase activity (+20.1%). Significant increases in shortening velocity at low and zero loads (+20.4%) were found in papillary muscles from treated animals when compared with the control muscles. These variations in enzymatic activity and shortening velocity could be related to the increase in the amount of the fast isomyosin V1, as shown by pyrophosphate gel electrophoresis. The negative force-frequency relation at steady state, typical of rat cardiac preparations, was observed in treated and control animals; its slope was, however, halved in hyperthyroid papillary muscles when compared with control ones. In accordance with this finding, the potentiating effect of a prolonged diastolic interval was significantly reduced in hyperthyroid papillary muscles. In the frame of an interpretation of the force interval relation on the basis of the excitation contraction coupling processes, these latter observations might indicate an enhanced activity of the sarcoplasmic reticulum. We conclude that thyroid hormone administration has a dual effect on cardiac contractility, on one hand regulating the synthesis of the different isomyosin and, on the other hand, stimulating the activity of the sarcoplasmic reticulum.
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PMID:The dual effect of thyroid hormones on contractile properties of rat myocardium. 297 Jun 23

The change in the isomyosin complement of avian and mammalian hearts was examined during the embryonic period in primary cultures of embryonic myocytes and in the cross-section of the adult ventricular wall. The type of myosin was determined by immunofluorescence using Abs specific for heavy chains of V1 and V3 isomyosins and by cytochemical staining for Ca2+ activated myosin ATPase. Our analysis indicates that the first isomyosin to appear in both chambers of avian heart is of the V3 type (HC beta). With advancing development, however, the atria initiate the expression of HC alpha and repress that of HC beta while the ventricle retains HC beta. In cultured myocytes derived from rat embryos cellular heterogeneity was detected in response to thyroid hormone. The cells are not synchronized in their response. Two populations are discernible with the minor one being thyroid hormone insensitive. Heterogeneity of the cellular populations was also seen in the left ventricle of adult rabbits. Myocytes with a similar isomyosin complement appear clustered with a predominance of V1 in the epicardium. Heterogeneous myocytes are, however, also frequently seen connected by an intercalated disc.
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PMID:Developmental aspects of cardiac contractile proteins. 299 29

The total ATPase activity of myosin and the values for the isozyme V1 have been measured in hearts from rats of different ages and with different levels of thyroid function. The contribution of V3 was calculated from the difference between total and V1 ATPase, neglecting the small contribution of V2. Hearts were quickly frozen after rapid removal from the animals in order to preserve the state of ATPase activity that existed in the intact animal, and ATPase activity was measured in thin sections of tissue by a microphotometric technique. In euthyroid hearts, although cAMP increases total myosin ATPase activity and the activity of V1, the cyclic nucleotide inhibits the ATPase activity of V3. In hearts from rats with developing hypothyroidism following thyroidectomy, the same occurs. After a sufficient period has elapsed after thyroidectomy for V1 to have practically disappeared, cAMP has no effect on ATPase activity, but the injection of thyroid hormone restores the effect. Total myosin ATPase activity is maintained relatively constant as the animal ages from 80 to 165 days and during the first 10-11 days following thyroidectomy even though the concentration of V1 is dropping. The explanation proposed for these observations is that myosin can exist in two different forms, only one of which can participate in the active generation of force. The transition between the two forms is regulated by a soluble factor that is itself controlled by the adrenergic system. The factor(s) involved in this regulatory mechanism is soluble and can be transferred between different thin sections cut from a frozen heart.
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PMID:Isozyme specific modification of myosin ATPase by cAMP in rat heart. 303 49


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