Na+,K+-ATPase enzyme units in lean and obese (ob/ob) thyroxine-injected mice.

1979 ◽  
Vol 237 (3) ◽  
pp. E265
Author(s):  
M H Lin ◽  
J G Vander Tuig ◽  
D R Romsos ◽  
T Akera ◽  
G A Leveille
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Large Dose ◽  
Binding Sites ◽  
Hormone Treatment ◽  
Obese Mice ◽  
Ouabain Binding ◽  
Hindlimb Muscles

The possible involvement of Na+,K+-ATPase in the etiology of obesity in the obese (ob/ob) mouse was explored. The number of Na+,K+-ATPase enzyme units in skeletal muscle, liver, and kidneys from 4- and 8-wk-old obese and lean mice was estimated from saturable [3H]ouabain binding to particulate fractions. Neither phenotype nor age altered the Kd value for ouabain binding in these three tissue preparations. The total number of [3H]ouabain binding sites in hindlimb muscles was 35--55% lower in 4- and 8-wk-old obese mice than in their lean counterparts. However, the total number of [3H]ouabain binding sites in liver and kidneys of obese mice was similar to values observed in their lean counterparts. Because it has been suggested that ob/ob mice are hypothyroid, we investigated the response of Na+,K+-ATPase in these mice to thyroid hormone treatment (approximately 5 microgram thyroxine/day for 2 wk). The number of [3H]ouabain binding sites in the three tissues increased in both obese and lean mice injected with this relatively large dose of thyroxine, but the obese mice were 2--3 times more responsive than lean mice.

scholarly journals Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone

1995 ◽  
Vol 311 (2) ◽  
pp. 567-573 ◽  
Author(s):  
P Chiarugi ◽  
G Raugei ◽  
R Marzocchini ◽  
T Fiaschi ◽  
C Ciccarelli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
State Level ◽  
K562 Cells ◽  
Hormone Treatment ◽  
Differential Regulation ◽  
Rapid Decrease ◽  
Differential Modulation ◽  
Hormone Administration ◽  
Specific Mrna

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

Effects of adrenal steroids on the concentration of Na+–K+ pumps in rat skeletal muscle

1997 ◽  
Vol 152 (1) ◽  
pp. 49-57 ◽  
Author(s):  
I Dørup ◽  
T Clausen
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Binding Sites ◽  
Total Concentration ◽  
Diaphragm Muscle ◽  
Minor Importance ◽  
Adrenal Steroids ◽  
Ouabain Binding ◽  
Old Rats ◽  
High Doses

Abstract Since adrenal steroids have been shown to upregulate the concentration of Na+–K+-ATPase in cardiac muscle, similar effects could be expected in skeletal muscle. Following infusion of dexamethasone (0·02–0·1 mg/kg per day) for 7 days in 10-week-old rats, the total concentration of [3H]ouabain-binding sites rose by up to 22–42% in soleus, extensor digitorum longus, gastrocnemius and diaphragm muscle. Dexamethasone produced no or minute changes in the Na+–K+ contents of skeletal muscle. In contrast, infusion with aldosterone (0·02–0·5 mg/kg per day) for 7 days produced hypokalemia and a graded reduction in the K+ content of skeletal muscle, which was closely correlated to a downregulation of the [3 H]ouabain-binding site concentration (r= 0·65–0·70; P<0·001). The results indicate that in skeletal muscle high doses of glucocorticoids upregulate the concentration of Na+–K+ pumps whereas mineralocorticoids induce a downregulation, which is secondary to the concomitant K+ deficiency. Since adrenalectomy produced no significant change in [3 H]ouabain-binding site concentration, basal levels of endogenous adrenal steroids seem to be of minor importance for the regulation of Na+–K+ pump concentration in skeletal muscle. Journal of Endocrinology (1997) 152, 49–57

scholarly journals Effects of semi-starvation and potassium deficiency on the concentration of [3H]ouabain-binding sites and sodium and potassium contents in rat skeletal muscle

1986 ◽  
Vol 56 (3) ◽  
pp. 519-532 ◽  
Author(s):  
Keld Kjeldsen ◽  
Maria Elisabeth Everts ◽  
Torben Clausen
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Soleus Muscle ◽  
Binding Sites ◽  
Total Concentration ◽  
Free Access ◽  
Rat Skeletal Muscle ◽  
Ouabain Binding ◽  
Digitalis Toxicity ◽  
Old Rats

1. Using vanadate-facilitated [3H]ouabain binding, the effect of semi-starvation on the total concentration of [3H]ouabain-binding sites was determined in samples of rat skeletal muscle. When 12-week-old rats were semi-starved for 1, 2 or 3 weeks on one-third to half the normal daily energy intake, the [3H]ouabain-binding site concentration in soleus muscle was reduced by 19, 24 and 25% respectively. In extensor digitorum longus, diaphragm and gastrocnemius muscles the decrease after 2 weeks of semi-starvation was 15, 18 and 17% respectively. The decrease was fully reversible within 3 d of free access to the diet. Complete deprivation of food for 5 d caused a reduction of 25% in soleus muscle [3H]ouabain-binding-siteconcentration. It was excluded that the reduction in [3H]ouabain binding was due to a reduced affinity of the binding site for [3H]ouabain.2. Semi-starvation of 12-week-old rats for 3 weeks caused a reduction of 45 and 53% in 3, 5, 3'-triiodothyronine (T3) and thyroxine (T4) levels respectively. As reduced thyroid hormone levels have previously been found to decrease [3H]ouabain-binding-siteconcentration in skeletal muscle, this points to the importance of T3 and T4 in the down-regulation of the [3H]ouabain-binding-siteconcentration in skeletal muscle with semi-starvation. Whereas potassium depletion caused a decrease in K content as well as in [3H]ouabain-binding-siteconcentration in skeletal muscles, semi-starvation caused only a tendency to a decrease in K content. Thus, K depletion is not a major cause of the reduction in [3H]ouabain-binding-siteconcentration with semi-starvation.3. Due to its high concentration of Na, K pumps, skeletal muscle has a considerable capacity for clearing K from the plasma as well as for the binding of digitalis glycosides. Semi-starvation causes a severe reduction in the total skeletal muscle pool of Na, K pumps and may therefore be associated with impairment of K tolerance and increased digitalis toxicity.

Insulin binding to individual rat skeletal muscles

1990 ◽  
Vol 259 (4) ◽  
pp. E517-E523 ◽  
Author(s):  
D. J. Koerker ◽  
I. R. Sweet ◽  
D. G. Baskin
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Binding Sites ◽  
Skeletal Muscles ◽  
Dissociation Constants ◽  
Binding Capacity ◽  
Fiber Type ◽  
Insulin Binding ◽  
Computer Assisted ◽  
Hindlimb Muscles

Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding.

Effects of thyroid hormone on UTP content and uridine kinase activity of rat heart and skeletal muscle

1980 ◽  
Vol 238 (5) ◽  
pp. E443-E449 ◽  
Author(s):  
B. J. Gertz ◽  
E. S. Haugaard ◽  
N. Haugaard
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Kinase Activity ◽  
Actinomycin D ◽  
Hormone Treatment ◽  
Subcutaneous Injections ◽  
Uridine Kinase ◽  
Single Intraperitoneal Injection ◽  
Uracil Nucleotide ◽  
Prior Administration

In rats made hyperthyroid by daily intramuscular injections of 250 microgram thyroxine (T4)/100 g body wt for 5 days, uridine kinase activity of extracts of psoas and cardiac muscle was markedly increased Vmax of the enzyme was elevated with no change in the apparent Km for uridine. In animals treated as above, significant increases in UTP and total uracil nucleotide contents were observed in heart and skeletal muscle. Twelve hours after a single intraperitoneal injection of 30 microgram/100 g body wt of 3,5,3'-triiodothyronine (T3), cardiac uridine kinase was significantly increased. Brain uridine kinase was unaffected by thyroid hormone treatment. In thyroidectomized rats, uridine kinase activity was lower than normal. The effect of thyroidectomy on uridine kinase activity was overcome by daily subcutaneous injections of 3 microgram T4/100 g body wt for 7 days. The rise in cardiac uridine kinase activity produced by T3 could be prevented by prior administration of actinomycin D.

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure

1997 ◽  
Vol 83 (1) ◽  
pp. 323-323 ◽  
Author(s):  
Joel G. Pickar ◽  
John P. Mattson ◽  
Steve Lloyd ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Chronic Heart Failure ◽  
Exercise Capacity ◽  
Binding Sites ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Ouabain Binding

Pickar, Joel G., John P. Mattson, Steve Lloyd, and Timothy I. Musch. Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure. J. Appl. Physiol. 83(1): 323–329, 1997.—Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed ∼180 days after surgery. Soleus and plantaris muscles were harvested, and Na+pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 ± 54 vs. 447 ± 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 ± 1 mmHg) compared with the sham-operated controls (1 ± 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 ± 12 vs. 175 ± 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 ± 12 vs. 147 ± 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

Skeletal muscle ouabain binding sites are reduced in rats with chronic heart failure

2002 ◽  
Vol 92 (6) ◽  
pp. 2326-2334 ◽  
Author(s):  
Timothy I. Musch ◽  
Swen Wolfram ◽  
K. Sue Hageman ◽  
Joel G. Pickar
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Oxygen Uptake ◽  
Binding Sites ◽  
Ouabain Binding ◽  
High Affinity ◽  
Lv Dysfunction ◽  
Run Time ◽  
Fast Twitch

Intrinsic skeletal muscle abnormalities decrease muscular endurance in chronic heart failure (CHF). In CHF patients, the number of skeletal muscle Na+-K+ pumps that have a high affinity for ouabain (i.e., the concentration of [3H]ouabain binding sites) is reduced, and this reduction is correlated with peak oxygen uptake. The present investigation determined whether the concentration of skeletal muscle [3H]ouabain binding sites found during CHF is related to 1) severity of the disease state, 2) muscle fiber type composition, and/or 3) endurance capacity. Four muscles were chosen that represented slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), and mixed fiber types. Measurements were obtained 8–10 wk postsurgery in 23 myocardial infarcted (MI) and 18 sham-operated control (sham) rats. Eighteen rats had moderate left ventricular (LV) dysfunction [LV end-diastolic pressure (LVEDP) < 20 mmHg], and five had severe LV dysfunction (LVEDP > 20 mmHg). Rats with severe LV dysfunction had significant pulmonary congestion and were likely in a chronic state of compensated congestive failure as indicated by an approximately twofold increase in both lung and right ventricle weight. Run time to fatigue and maximal oxygen uptake (V˙o 2 max) were significantly reduced (↓39 and ↓28%, respectively) in the rats with severe LV dysfunction and correlated with the magnitude of LV dysfunction as indicated by LVEDP (run time: r = 0.60, n = 21, P < 0.01 and V˙o 2 max: r = 0.93, n = 13, P < 0.01). In addition, run time to fatigue was significantly correlated withV˙o 2 max ( r = 0.87, n = 15, P < 0.01). The concentration of [3H]ouabain binding sites (Bmax) was significantly reduced (21–28%) in the three muscles comprised primarily of oxidative fibers [soleus: 259 ± 14 vs. 188 ± 17; plantaris: 295 ± 17 vs. 229 ± 18; red portion of gastrocnemius: 326 ± 17 vs. 260 ± 14 pmol/g wet tissue wt]. In addition, Bmax was significantly correlated withV˙o 2 max (soleus: r = 0.54, n = 15, P < 0.05; plantaris: r = 0.59, n = 15, P < 0.05; red portion of gastrocnemius: r = 0.65, n = 15, P < 0.01). These results suggest that downregulation of Na+-K+ pumps that possess a high affinity for ouabain in oxidative skeletal muscle may play an important role in the exercise intolerance that attends severe LV dysfunction in CHF.

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