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 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

The atrophy produced by endocrine disorders is primarily due to alterations in protein and carbohydrate metabolism. Type II muscle fibers are more severely affected than are Type I fibers. Steroid myopathy and the myopathy associated with excess ACTH have a typical pattern of proximal weakness affecting the legs more than the arms. Steroid myopathy is usually not apparent until other signs of glucocorticoid excess are present. Treatments of steroid myopathy are as follows: Lower the dose of steroid, use a nonfluorinated glucocorticoid, and exercise or physical therapy. Adrenal insufficiency produces generalized weakness, muscle cramping, and fatigue in 50 per cent of patients. Some patients also develop hyperkalemic paralysis. The treatment is hormone replacement. Thyrotoxicosis produces myopathy caused by net protein catabolism, accelerated basal metabolic rate and impaired carbohydrate metabolism. Shortening of contraction time may result from accelerated myosin ATPase activity and enhanced calcium uptake by the sarcoplasmic reticulum. Depolarization of the muscle fiber and impaired Na-K activity in muscle may predispose to thyrotoxic periodic paralysis. Neuromuscular presynaptic impairment may account for the worsening of myasthenia gravis by thyrotoxicosis. In hypothyroidism, impaired energy metabolism may limit force generation. Slow contraction and relaxation reflect reduction in myosin ATPase activity and impaired calcium uptake by the sarcoplasmic reticulum. Treatment for thyroid-associated muscle disorders is restoration of a euthyroid state. Muscle weakness associated with hypopituitarism is due to loss of thyroid and adrenal cortical hormones. Children require growth hormone for muscle development. T3 and growth hormone synergize to maintain normal protein synthesis. Primary and secondary hyperparathyroidism and osteomalacia are often associated with proximal weakness and fatigability. The myopathy improves with restoration of normal PTH levels and vitamin D replacement. Hypoparathyroidism and pseudohypothyroidism are associated with tetany. Tetany is worsened by alkalosis and is treated by calcium and magnesium replacement.
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PMID:Endocrine myopathies. 306 2

The influence of hyper- and hypothyroidism on atrial and ventricular myosin structure and Ca2+-activated ATPase activity has been analyzed in adult mini-pigs. Whereas no difference could be demonstrated between hypo- and euthyroid ventricular myocardium, Ca2+-activated ATPase activity was significantly higher in the hyperthyroid than in the hypo- or euthyroid state. Using pyrophosphate electrophoresis and isoelectric focusing of subfragment 1 this could be ascribed to an additional ventricular myosin in the hyperthyroid myocardium. Atrial myosin ATPase activity and structure were not influenced by the thyroid state of the animals. These results present evidence that thyreotoxicosis induces an additional isomyosin in the pig ventricular myocardium, albeit to a lesser degree than in the rodent heart. The lacking difference between the hypothyroid and the euthyroid states indicates that a myosin with a lower enzymatic activity than the normal ventricular myosin is not synthesized in the heart of higher mammals.
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PMID:Influence of the thyroid state on myocardial myosin in the adult pig heart. 315 68

Studies were conducted to determine if the level of cardiac Ca+2-activated myosin ATPase activity and ventricular myosin isoenzyme distribution are influenced by both T3 administration and fructose feeding. Previous studies have shown that in the cardiac ventricle of hypothyroid rats, only myosin V3 is present, and the Ca+2-activated myosin ATPase activity is markedly decreased. Hypothyroid [thyroidectomized (Tx)] rats were fed a diet containing 60% fructose or a regular diet (47% complex carbohydrates) for 4 weeks. Fructose feeding of hypothyroid rats led to a significant increase in Ca+2-activated myosin ATPase activity (Tx regular diet, 0.33 +/- 0.02 mumol Pi/mg protein X min; Tx fructose diet, 0.54 +/- 0.04 mumol Pi/mg protein X min). In addition, myosin V1 was detectable in the heart of fructose-fed Tx rats, but was absent in Tx rats on the regular diet. To determine if fructose had an effect of similar magnitude in animals of different thyroid states, Tx rats were injected with 0.075, 0.150, 0.225, and 0.300 micrograms T3/100 g BW daily and placed on fructose or regular diets. The fructose-induced increase in Ca+2-myosin ATPase activity was between 24-27% in Tx rats receiving 0-0.15 micrograms T3/100 g BW daily. In animals receiving 0.225 and 0.300 micrograms T3/100 g BW daily, fructose feeding did not induce a significant increase in myosin ATPase activity. This is due to the fact that the Ca+2-activated myosin ATPase activities of euthyroid and hyperthyroid animals are not significantly different from each other. In hypothyroid rats receiving a 60% glucose diet, Ca+2-myosin ATPase activity showed a significant 20% increase above the value in regular diet-fed Tx rats. Fructose- and glucose-induced changes in Ca+2-myosin ATPase activity occurred in the absence of changes in thyroid hormone or insulin levels. Our findings may indicate that cardiac carbohydrate consumption influences the predominance of ventricular myosin isoenzymes in the rat heart.
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PMID:Myosin isoenzyme distribution and Ca+2-activated myosin ATPase activity in the rat heart is influenced by fructose feeding and triiodothyronine. 315 9

We have analyzed the effect of 6-propylthiouracil-induced hypothyroidism on neonatal fiber type differentiation in the rat soleus muscle. Body weight, total soleus fiber number, histochemical fiber type differentiation, and morphometry were determined at 7, 14, 21, and 28 days. Neonatal hypothyroidism (1) inhibits the apparent approximately 50% increase in soleus muscle fiber number occurring at 14-21 days, (2) blocks the transformation of type 2C to type 2A fibers occurring between 14 and 21 days, (3) preferentially inhibits the increase in type 2 fiber diameter, and (4) retards the development of sarcoplasmic reticulum. Immature muscle fibers reveal type 1 and type 2 fiber myosin adenosine triphosphatase (ATPase) differentiation at pH 10.3, which drops to pH 9.4 with maturation. No myosin ATPase differentiation was found at pH 9.4 in the hypothyroid animals, even at 28 days.
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PMID:Postnatal histochemical fiber type differentiation in normal and hypothyroid rat soleus muscle. 405 73

Previous studies have shown that diabetes mellitus leads in rats to a 45% decrease in cardiac Ca++ activated myosin ATPase, a change in myosin isoenzyme distribution and a lowering of plasma T4 and T3 levels. Hypothyroidism causes similar changes in myosin ATPase and myosin isoenzyme distribution. We determined if thyroid hormone administration in physiological replacement dose (0.3 microgram T3/100 g BW) or pharmacological doses (3 micrograms T3/100 g BW and 10 micrograms T4/100 g BW) can normalize myosin ATPase and isoenzyme distribution in diabetic rats. Control animals have a Ca++ myosin ATPase activity of 1.23 +/- 0.14 mumol Pi/mg protein/min and myosin V1 represented 70% and myosin V3 15% of total myosin. Four weeks after streptozotocin administration myosin ATPase was 0.61 +/- 0.14, and myosin V3 represented 67% of total myosin. Administration of 0.3 microgram T3/100 g BW/day for four weeks to diabetic animals resulted in no significant increase in myosin ATPase (0.69 +/- 0.07 mumol Pi/mg protein/min) or in myosin isoenzyme distribution. In contrast, administration of 3 micrograms T3/100 g BW/day or 10 micrograms T4/100 g BW/day for 4 wk led to a normalization of myosin ATPase activity (for T3 1.03 +/- 0.18, for T4 1.06 +/- 0.15). In addition the myosin isoenzyme distribution pattern normalized. These findings may point to a diminished thyroid hormone responsiveness in diabetic rats or could result from diabetes related disturbances of cellular metabolism, which are normalized by pharmacologic doses of thyroid hormone.
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PMID:Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. 621 Aug 24

The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypothyroidism or hyperthyroidism. Triiodothyronine (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 independently 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. 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, T3 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. The pathophysiologic basis for myxedema is the opposite of that discussed for the hyperthyroid heart. In addition to decreased direct effects of thyroid hormone in cardiac myocytes, indirect effects occur through decreases in peripheral oxygen consumption and changes in hemodynamic parameters. Myofibrillar swelling with loss of striation and interstitial fibrosis occurs on histologic examination of hypothyroid hearts. In addition, accumulation of mucopolysaccharide substances (Glycosaminoglycans) can be demonstrated. On electron microscopic examination, mitochondria show disruption and lipid inclusion. Cardiac papillary muscle obtained from animals with hypothyroidism shows a depression of the force velocity curve and reduced rate of tension development, indicating significant contractile abnormalities. In patients with hypothyroidism, a true enhanced incidence of hypertension (increased peripheral vascular resistance) has been found. In addition, hypercholesterolemia and impairment of fatty acid mobilization are associated with myxedema and present additional risk factors for the development of atherosclerotic cardiovascular disease.
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PMID:[Cardiovascular effects of thyroid hormones]. 906 69


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