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)

Amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3', 5'-diiodobenzoyl-benzofurane) is an antiarrhythmic drug which increases serum T4 and rT3 levels in patients and lowers serum T3 levels. To investigate its effects on T4 metabolism and its cardiac action, we fed amiodarone to male Fisher rats at doses of 5, 15, and 45 mg/kg BW X day; controls received potassium iodide for 4-7 weeks, and another group received sodium ipodate. At 4 weeks, amiodarone caused a dose-dependent increase in the serum T4 concentration and a slight reduction of serum TSH without a change in the serum T3 concentration. These changes were not present at 7 weeks. Sodium ipodate raised serum T4 concentrations at both times. Rats treated with T4 (150 micrograms/kg BW X day) to suppress thyroidal secretion of hormone and with amiodarone (15 mg/kg) had marked reduction of serum T3 concentrations compared with controls receiving T4 without amiodarone. Liver homogenates from rats treated with amiodarone showed marked reduction on T4 5'-monodeiodinase activity in a dose-related manner. Amiodarone added to liver homogenates in vitro at concentrations of 0.001-1 mM did not inhibit T3 production from T4, whereas ipodate added in vitro (0.01-1 mM) did inhibit T3 production. Rats treated with amiodarone showed a lowering of the resting heart rate and a reduction of the increment in heart rate after iv isoproterenol administration. The cardiac Ca++ myosin ATPase activity was reduced in rats receiving amiodarone (45 mg/kg) compared with that in controls. The data indicate that rats treated with amiodarone have reduced peripheral conversion of T4 to T3 owing to impaired hepatic T4 5'-monodeiodinase activity. In addition, these rats have slowing of heart rate and reduction of cardiac Ca++ myosin ATPase activity. These findings are consistent with the hypothesis that amiodarone blocks some effects of thyroid hormone on the heart, but additional studies are needed to test this hypothesis.
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PMID:The effects of amiodarone on serum thyroid hormones and hepatic thyroxine 5'-monodeiodination in rats. 661 81

Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic for 6-10 weeks were treated with PZI insulin for 2, 6, 10, or 28 days and the mechanical performance of their left ventricular papillary muscles was compared to that of untreated diabetics and age-matched controls; cardiac contractile protein enzymatic activity was also measured. Neither 2 nor 6 days of therapy had any effects on the depressed cardiac muscle performance of diabetic animals, although plasma glucose concentration was restored to normal. By 10 days of therapy, recovery of mechanical performance was nearly complete, and by 28 days of therapy, complete reversal of the altered myocardial mechanics was observed. Crystalline insulin added to the bath (9 mU/ml) had no effect on myocardial mechanics in either diabetics or controls. A gradual recovery of actomyosin and myosin ATPase activity in the hearts of insulin-treated diabetic animals was also found, complementing the mechanical studies. In addition to demonstrating a gradual but complete reversibility of the abnormalities in papillary muscle function in diabetic rats (although control of hyperglycemia was less than ideal), this study confirms that this model of a cardiomyopathy is not a result of streptozotocin-induced cardiac toxicity. Additional data are provided indicating that depressed thyroid hormone levels in diabetic rats are not responsible for the mechanical changes observed.
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PMID:Reversibility of diabetic cardiomyopathy with insulin in rats. 703 May 13

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

The changes of myosin isoform pattern and of its associated light chains in relation to the myosin ATPase profile were analysed in different muscles of the hypothyroidian amphibian Pleurodeles waltlii submitted to terrestrial stepping, using electrophoretic and histochemical techniques. These changes were specific to the muscle type but appeared globally characterized by a type-IIB to type-IIA/I fibre transition associated with a transition from fast to intermediate and/or slow myosin isoforms. These results are similar to the effects of endurance training on locomotor muscles of mammals. The diaphragm of experimental animals was also characterized by a complete disappearance of the larval myosin isoforms which were detected in the diaphragm of control animals. The myosin pattern of ventricular muscle did not change following terrestrial stepping. This work indicates that thyroid hormone does not regulate the muscle adaptations that occur following terrestrial stepping and suggests a more complex mechanism of regulation in which innervation could be implicated.
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PMID:Analysis of muscle adaptations to terrestrial stepping in the Urodelan amphibian Pleurodeles waltlii. 959 31

Recycling endosomes in astrocytes show hormone-regulated, actin fiber-dependent delivery to the endosomal sorting pool. Recycling vesicle trafficking was followed in real time using a fusion protein composed of green fluorescent protein coupled to the 29-kDa subunit of the short-lived, membrane-bound enzyme type 2 deiodinase. Primary endosomes budded from the plasma membrane and oscillated near the cell periphery for 1-4 min. The addition of thyroid hormone triggered the processive, centripetal movement of the recycling vesicle in linear bursts at velocities of up to 200 nm/s. Vesicle migration was hormone-specific and blocked by inhibitors of actin polymerization and myosin ATPase. Domain mapping confirmed that the hormone-dependent vesicle-binding domain was located at the C terminus of the motor. In addition, the interruption of normal dimerization of native myosin 5a monomers inactivated vesicle transport, indicating that single-headed myosin 5a motors do not transport cargo in situ. This is the first demonstration of processive hormone-dependent myosin 5a movement in living cells.
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PMID:Real-time visualization of processive myosin 5a-mediated vesicle movement in living astrocytes. 1147 Jul 81


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