Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify the mechanism of the different sensitivity of the adrenoceptors between normal and hypothyroid rats, cyclic AMP levels in the liver and heart were measured after the administration of phenylephrine, isoproterenol, epinephrine and methoxamine. Cyclic AMP increased in all cases, but the extent of its increment in the heart was much less than that in the liver. Phentolamine and propranolol showed only a partial inhibition of cyclic AMP elevation by the agonists in the liver from normal and hypothyroid rat. On the other hand, propranolol blocked completely the effect of the agonists on the heart from both groups. It was also observed that cyclic AMP increased in adrenalectomized rats after the injection of the adrenergic agonists. The basal activity of protein kinase in hypothyroid status was slightly lower than that in the normal, but this enzyme was stimulated in the presence of cyclic AMP in vitro. These results suggest that the function of beta-adrenoceptor remained normal even in hypothyroidism and responded well to isoproterenol and epinephrine. It is also indicated that the increased sensitivity of alpha-adrenoceptor to phenylephrine in the hy pothyroid atria previously observed is probably in part independent of the mechanism mediated by cyclic AMP.
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PMID:Effect of adrenergic agonists on the cyclic AMP level in the liver and heart from normal and hypothyroid rats. 18 22

Protein kinase activities were determined in liver from normal, thyroidectomized and triiodothyronine (T3)-treated rats. Changes related to thyroid hormone were observed in cytosol and nuclear protein kinase activities. When protamine was used as substrate for phosphorylation, thyroidectomy induced a decrease of protein kinase activity associated with nuclei but an increase of activity was found in the cytosol. Fifteen hours after injection of T3 the levels in nuclei and cytosol were restored to normal. When casein was used as substrate, hypothyroidism led to a lowering of protein kinase activity in both fractions and T3 treatment augmented the activity in both. These studies suggest that thyroid hormones modify hepatic protein kinase activity. Results differ depending upon the substrate used. The hormones also appear to alter the subcellular distribution of some protein kinase activities.
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PMID:Liver protein kinase activity and triiodothyronine. 83 87

The regulatory effect of thyroid hormone on cardiac protein kinase activity and ATP hydrolysis was studied in developing rats. Experimental hypothyroidism induced by a single intraperitoneal injection of 200 muCi of 131I led to a significant impairment of body and heart growth and elevated the activity of membrane-bound protein kinase (measured in the absence of cyclic AMP). However, a slight (11%) but statistically non-significant decrease was observed in soluble protein kinase activity in hearts of hypothyroid rats. Furthermore, thyroid deficiency produced in neonatal life significantly decreased (34%) the rate of cardiac ATP hydrolysis. Treatment of thyroidectomized animals with L-triiodothyronine initiated early in life produced a time-dependent increase in heart weight as well as the activity of soluble protein kinase and the rate of ATP hydrolysis in cardiac tissue. Maximal rise in these parameters was observed in hypothyroid rats receiving L-triiodothyronine treatment for 24 days beginning from 7 days after radioiodine injection. These animals also showed a marked cardiac hypertrophy. In contrast, replacement therapy with L-triiodothyronine produced a decrease in the activity of the membrane-bound protein kinase, which seemed to be inversely proportional to the duration of L-triiodothyronine treatment. Our data provide evidence suggesting that thyroid hormone plays an important role in controlling ATP turnover in hearts of developing rats.
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PMID:Effect of radio-thyroidectomy and thyroid hormone replacement therapy on cardiac protein kinase activity and ATP hydrolysis. 121 63

We investigated the influence of the thyroid hormone status on the levels of protein kinases C (PKC) and A (PKA) in the soluble fraction of rat liver. The immunodetectable PKC level in hypothyroid liver was elevated 7.7-fold, whereas the phorbol-ester binding capacity and the immunodetectable alpha-PKC level were increased 2.4- and 2.6-fold, respectively. Conversely, in hypothyroid livers the abundance of the regulatory type I and the catalytic subunits of PKA were lowered to 42% of the euthyroid level as determined by immunoblotting and by measuring the substrate specific phosphorylation rate of PKA. These changes in the PKC and PKA levels were reversible upon treatment with 0.5 microgram T4/100 g body weight for 2-21 days. The thyroid state dependent alterations in hepatic PKC and PKA levels may be responsible for the known changes in the response of hepatocytes to other hormonal stimuli in hypothyroidism.
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PMID:Effect of hypothyroidism and thyroid hormone replacement on the level of protein kinase C and protein kinase A in rat liver. 203 57

The effects of hypothyroidism on glycogen metabolism in rat skeletal muscle were studied using the perfused rat hindlimb preparation. Three weeks after propylthiouracil treatment, serum thyroxine was undetectable and muscle glycogen and Glc-6-P were decreased. Basal and epinephrine-stimulated phosphorylase a and phosphorylase b kinase activities were also significantly reduced, as were epinephrine-stimulated cAMP accumulation and cAMP-dependent protein kinase activity. Conversely, basal and epinephrine-stimulated glycogen synthase I activities were significantly higher while the Ka of the enzyme for Glc-6-P was lower in hypothyroid animals. Propylthiouracil-treated rats also had increased phosphoprotein phosphatase activities towards phosphorylase and glycogen synthase and decreased activity of phosphatase inhibitor 1. beta-Adrenergic receptor binding and basal and epinephrine-stimulated adenylate cyclase activities were reduced in muscle particulate fractions from hypothyroid rats. Administration of triiodothyronine to rats for 3 days after 3 weeks of propylthiouracil treatment restored the altered metabolic parameters to normal. It is proposed that the decreased beta-adrenergic responsiveness of the enzymes of glycogen metabolism in hypothyroid rat skeletal muscle is due to increased activity of phosphoprotein phosphatases and to reduced beta-adrenergic receptors and adenylate cyclase activity.
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PMID:Effects of altered thyroid status on beta-adrenergic actions on skeletal muscle glycogen metabolism. 299 Dec 89

Cyclic-AMP-dependent protein kinase from the soluble fraction of parotid glands of hypothyroid rats was partially purified. Its isozyme distribution and kinetic properties were similar to those of euthyroid rats. Electrophoresis of 100 microliters portions at 20 mA per slab revealed that an endogenous protein (mol. wt 68,000) was specifically phosphorylated in hypothyroidism; this protein was not found in euthyroid rats. In the presence of cyclic AMP, there was stimulated phosphorylation of euthyroid-soluble proteins with molecular weights of 115,000, 98,000, 57,000, 50,000, 44,000, 33,000 and 19,000, and of proteins from hypothyroid rats with weights of 115,000, 98,000, 60,000, 50,000, 33,000 and 19,000. Tolbutamide reduced incorporation of 32Pi into soluble proteins from both groups. However, cyclic AMP still induced phosphorylation in euthyroid preparations in the presence of tolbutamide, but its effect was markedly reduced in the hypothyroid state. These differences in endogenous protein phosphorylation may have different effects on amylase release induced by beta-adrenergic stimulation.
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PMID:Cyclic-AMP-dependent protein phosphorylation in the soluble fraction of parotid glands from rats with drug-induced hypothyroidism. 301 39

The role of thyroid hormones in the metabolic adaptation to starvation was investigated in vivo. Glucose production, measured by tracer technique, was enhanced in hyperthyroid (185%) and reduced in hypothyroid (39%) 48-hour starved rats (euthyroid control = 100%). Urinary nitrogen excretion was increased in hyperthyroidism (132%) and decreased in hypothyroidism (70%). Compared with euthyroid controls (=100%) significant alterations for the following regulatory parameters of hepatic gluconeogenesis were observed: 1) tissue cAMP (124%/91%) and protein kinase activation (132%/90%), with a corresponding crossover between pyruvate and P-enolpyruvate (-/+/+/-); 2) pyruvate carboxylase (165%/60%), P-enolpyruvate carboxykinase (140%/82%) and fructose-1.6-bis-P-phosphatase activity (99%/61%), and 3) tissue content of the glucogenic amino acids: alanine (187%/66%) and glutamate (187%/88%), aspartate (179%/68%) and glutamate (137%/75%), as well as of oxaloacetate (254%/66%) and malate (164%/104%). The observed alterations in hepatic oligomycine-sensitive oxygen consumption in hyper- (161%) and hypothyroidism (51%) were related to the measured concentration of the intermediates of the citric acid cycle, the energy state and the mitochondrial redox state. In summary, the different rates of hepatic glucose production in hyper- and hypothyroid starved rats observed in vivo can be ascribed to 1) cAMP content, 2) gluconeogenic key enzyme activities, 3) glucogenic precursor supply and 4) cofactor (ATP) availability.
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PMID:Starvation-induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo. 626 36

Forskolin increased cyclic AMP accumulation in isolated adipocytes and markedly potentiated the elevation of cyclic AMP due to isoproterenol. In adipocyte membranes, forskolin stimulated adenylate cyclase activity at concentrations of 0.1 microM or greater. Forskolin did not affect the EC50 for activation of adenylate cyclase but did increase the maximal effect of isoproterenol. Neither the soluble nor particulate low-Km cyclic AMP phosphodiesterase activity was affected by forskolin. Low concentrations of forskolin (0.1-1.0 microM), which significantly elevated cyclic AMP levels, did not increase lipolysis, whereas similar increases in cyclic AMP levels due to isoproterenol elevated lipolysis. Forskolin did not inhibit the activation of triacylglycerol lipase by cyclic AMP-dependent protein kinase or the subsequent hydrolysis of triacylglycerol. Higher concentrations of forskolin (10-100 microM) did increase lipolysis. Both the increased cyclic AMP production and lipolysis due to forskolin were inhibited by the antilipolytic agents insulin and N6-(phenylisopropyl)adenosine. Hypothyroidism reduced the ability of forskolin to stimulate cyclic AMP production and lipolysis. These results indicate that forskolin increases cyclic AMP production in adipocytes through an activation of adenylate cyclase. Lipolysis is activated by forskolin but at higher concentrations of total cyclic AMP than for catecholamines.
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PMID:Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes. 628 66

The influence of thyroid hormones on the adrenergic regulation of lipolysis was studied in isolated adipocytes removed from the gluteal region of hyper- and hypothyroid women and compared in adipocytes from euthyroid normal women. Noradrenaline significantly enhanced lipolysis in hyperthyroid patients, whereas noradrenaline inhibited lipolysis in hypothyroid patients compared to that in controls. Moreover, beta-adrenergic sensitivity and responsiveness were 10- and 2-fold increased, respectively, in hyperthyroid patients. In hypothyroid patients, beta-adrenoceptor responsiveness was reduced by 50%, whereas beta-adrenergic sensitivity remained unchanged compared with that in controls. Furthermore, the alpha 2-adrenergic and adenosine-induced antilipolytic effects were similar in all thyroid states. The lowered beta-adrenergic responsiveness seen in hypothyroidism could be mimicked by agents acting at the levels of phosphodiesterase (enprofylline), adenylate cyclase (forskolin) and protein kinase (dibutyryl cAMP). In hyperthyroidism, the increased beta-adrenergic sensitivity and responsiveness were not seen when lipolysis was stimulated at the adenylate cyclase, phosphodiesterase, or protein kinase levels. There was no change in the numbers of adipocyte beta- and alpha 2-adrenoceptors in hypothyroidism. However, the number of beta-adrenergic binding sites was doubled, whereas the fraction and affinities of isoprenaline high affinity sites remained unchanged in hyperthyroidism. Thus, the influence of thyroid hormone on catecholamine-stimulated lipolysis in man acts through different mechanisms when adipocytes are exposed to high or low levels of thyroid hormones. In hyperthyroidism, lipolysis adapts to increasing energy demands through an increase in the beta-adrenoceptor number and, thus, a more effective coupling of the adenylate-cyclase complex. In hypothyroidism, the low lipolytic effect of catecholamines seems to be mainly due to an impairment at the protein kinase level or to the hormone-sensitive lipase itself.
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PMID:Adrenergic regulation of lipolysis in fat cells from hyperthyroid and hypothyroid patients. 815 18

The effect of thyroid status on myocardial function and accompanying alterations in the expression of specific genes has been well defined in animals. However, the effects of thyroid hormones on the basal phosphorylation of key cardiac regulatory proteins, which may also contribute to alterations in myocardial function, have not been defined. The present study concerns the phosphorylation status of myofibrillar proteins in hearts from hyperthyroid, euthyroid and hypothyroid rats. Hyperthyroidism was produced by daily subcutaneous injections of L-triiodothyronine, while hypothyroidism was induced with an iodine-deficient diet and KClO4. Two different approaches were used to study changes in the basal phosphorylation levels of troponin I and C protein: 1) direct measurement of the 32P-label associated with these proteins, using intact, beating hearts perfused with [32P]orthophosphate-labeled Krebs buffer; 2) indirect measurement by the back-phosphorylation technique with [gamma-32P]ATP and the catalytic subunit of cAMP-dependent protein kinase in vitro. Measurements of left ventricular contraction (+dP/dt and -dP/dt) were significantly higher in hyperthyroid than in euthyroid animals and this was associated with increases in basal phosphorylation levels of both troponin I and C protein in the myofibrils. In hypothyroid animals, both +dP/dt and -dP/dt were significantly lower than in euthyroid animals and this was associated with decreases in basal phosphorylation levels of troponin I and C protein. The changes in the phosphorylation status of troponin I or C protein correlated with the changes in the speed of myocardial relaxation (-dP/dt) in response to the altered thyroid states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of thyroid status on basal phosphorylation of cardiac myofibrillar phosphoproteins in rats. 820 92


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