scholarly journals Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina K. Selivanova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova
Keyword(s):  
Skeletal Muscle ◽  
Kinase Inhibitors ◽  
Isometric Force ◽  
Rho Kinase ◽  
Integrin Αvβ3 ◽  
Acute Effects ◽  
Rat Skeletal Muscle ◽  
Subsequent Decrease ◽  
Adrenoceptor Agonist ◽  
Male Wistar Rats

Aim: Hyperthyroidism is associated with a decreased peripheral vascular resistance, which could be caused by the vasodilator genomic or non-genomic effects of thyroid hormones (TH). Non-genomic, or acute, effects develop within several minutes and involve a wide tissue-specific spectrum of molecular pathways poorly studied in vasculature. We aimed to investigate the mechanisms of acute effects of TH on rat skeletal muscle arteries.Methods: Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting).Results: Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α1-adrenoceptor agonist methoxamine. The effect of T4 was more prominent than T3 and not affected by iopanoic acid, an inhibitor of deiodinase 2. Endothelium denudation abolished the effect of T3, but not T4. Integrin αvβ3 inhibitor tetrac abolished the effect of T4 in endothelium-denuded arteries. T4 weakened methoxamine-induced elevation of phospho-MLC2 (Ser19) content in arterial samples. The effect of T4 in endothelium-denuded arteries was abolished by inhibiting ERK1/2 activation with U0126 as well as by ILK inhibitor Cpd22 but persisted in the presence of Src- or Rho-kinase inhibitors (PP2 and Y27632, respectively).Conclusion: Acute non-genomic relaxation of sural arteries induced by T3 is endothelium-dependent and that induced by T4 is endothelium-independent. The effect of T4 on α1-adrenergic contraction is stronger compared to T3 and involves the suppression of extracellular matrix signaling via integrin αvβ3, ERK1/2 and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.

scholarly journals Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Damian Jozef Flis ◽  
Robert Antoni Olek ◽  
Jan Jacek Kaczor ◽  
Ewa Rodziewicz ◽  
Malgorzata Halon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cholesterol Metabolism ◽  
Exercise Group ◽  
Mitochondrial Swelling ◽  
Control Group ◽  
Rat Skeletal Muscle ◽  
Muscle Mitochondria ◽  
Caveolin 1 ◽  
Male Wistar Rats ◽  
Exercise Induced

The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

scholarly journals Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

2018 ◽  
Vol 17 (4) ◽  
pp. 23-32
Author(s):  
D. K. Gaynullina ◽  
E. K. Selivanova ◽  
A. P. Sharova ◽  
O. S. Tarasova
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Rho Kinase ◽  
Antithyroid Drug ◽  
Free Water ◽  
Control Group ◽  
Resistance Arteries ◽  
Adult Rats ◽  
Contractile Responses ◽  
Male Wistar Rats

Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.

scholarly journals Chronic and acute effects of thiazolidinediones BM13.1258 and BM15.2054 on rat skeletal muscle glucose metabolism

1999 ◽  
Vol 128 (6) ◽  
pp. 1141-1148 ◽  
Author(s):  
C Fürnsinn ◽  
B Brunmair ◽  
M Meyer ◽  
S Neschen ◽  
R Furtmüller ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Acute Effects ◽  
Rat Skeletal Muscle

scholarly journals Increased AS160 phosphorylation, but not TBC1D1 phosphorylation, with increased postexercise insulin sensitivity in rat skeletal muscle

2009 ◽  
Vol 297 (1) ◽  
pp. E242-E251 ◽  
Author(s):  
Katsuhiko Funai ◽  
George G. Schweitzer ◽  
Naveen Sharma ◽  
Makoto Kanzaki ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Exercise Bout ◽  
Rab Gtpase ◽  
Rat Skeletal Muscle ◽  
Gtpase Activating Proteins ◽  
Male Wistar Rats ◽  
Insulin Dependent ◽  
Experimental Protocols

A single exercise bout can increase insulin-independent glucose transport immediately postexercise and insulin-dependent glucose transport (GT) for several hours postexercise. Akt substrate of 160 kDa (AS160) and TBC1D1 are paralog Rab GTPase-activating proteins that have been proposed to contribute to these exercise effects. Previous research demonstrated greater AS160 and Akt threonine phosphorylation in rat skeletal muscle at 3–4 h postexercise concomitant with enhanced insulin-stimulated GT. To further probe whether these signaling events or TBC1D1 phosphorylation were important for the enhanced postexercise insulin-stimulated GT, male Wistar rats were studied using four experimental protocols (2-h swim exercise, differing with regard to timing of muscle sampling and whether food was provided postexercise) that were known to vary in their influence of insulin-independent and insulin-dependent GT postexercise. The results indicated that, in isolated rat epitrochlearis muscle, 1) elevated phosphorylation of AS160 (measured using anti-phospho-Akt substrate, PAS-AS160, and phosphospecific anti-Thr642-AS160, pThr642-AS160) consistently tracked with elevated insulin-stimulated GT; 2) PAS-TBC1D1 was not different from sedentary values at 3 or 27 h postexercise, when insulin sensitivity was increased; 3) insulin-stimulated Akt activity was not increased postexercise in muscles with increased insulin sensitivity; 4) PAS-TBC1D1 was increased immediately postexercise, when insulin-independent GT was elevated, and reversed at 3 and 27 h postexercise, when insulin-independent GT was also reversed; and 5) there was no significant effect of exercise or insulin on total abundance of AS160, TBC1D1, Akt, or GLUT4 protein with any of the protocols. The results are consistent with increased AS160 phosphorylation (PAS-AS160 or pThr642-AS160) but not increased PAS-TBC1D1 or Akt activity, which is important for increased postexercise insulin-stimulated GT in rat skeletal muscle. They also support the idea that increased TBC1D1 phosphorylation may play a role in the insulin-independent increase in GT postexercise.

scholarly journals Leucine Supplementation Decreases HDAC4 Expression and Nuclear Localization in Skeletal Muscle Fiber of Rats Submitted to Hindlimb Immobilization

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2582
Author(s):  
Paula K. N. Alves ◽  
André Cruz ◽  
William J. Silva ◽  
Siegfried Labeit ◽  
Anselmo S. Moriscot
Keyword(s):  
Skeletal Muscle ◽  
Target Genes ◽  
Marked Decrease ◽  
Mrna Levels ◽  
Rna Seq ◽  
Rat Skeletal Muscle ◽  
Leucine Supplementation ◽  
Male Wistar Rats ◽  
Histone Deacetylase 4 ◽  
The Impact

In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (~280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (~50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine.

β2-Agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol

2002 ◽  
Vol 283 (6) ◽  
pp. R1386-R1394 ◽  
Author(s):  
James G. Ryall ◽  
Paul Gregorevic ◽  
David R. Plant ◽  
Martin N. Sillence ◽  
Gordon S. Lynch
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Therapeutic Potential ◽  
Contractile Function ◽  
Isometric Force ◽  
Cross Sectional ◽  
Skeletal Muscle Wasting ◽  
Adrenoceptor Agonist ◽  
Ergogenic Effects ◽  
Β2 Agonist

Potential treatments for skeletal muscle wasting and weakness ideally possess both anabolic and ergogenic properties. Although the β2-adrenoceptor agonist clenbuterol has well-characterized effects on skeletal muscle, less is known about the therapeutic potential of the related β2-adrenoceptor agonist fenoterol. We administered an equimolar dose of either clenbuterol or fenoterol to rats for 4 wk to compare their effects on skeletal muscle and tested the hypothesis that fenoterol would produce more powerful anabolic and ergogenic effects. Clenbuterol treatment increased fiber cross-sectional area (CSA) by 6% and maximal isometric force (Po) by 20% in extensor digitorum longus (EDL) muscles, whereas fiber CSA in soleus muscles decreased by 3% and Po was unchanged, compared with untreated controls. In the EDL muscles, fenoterol treatment increased fiber CSA by 20% and increased Po by 12% above values achieved after clenbuterol treatment. Soleus muscles of fenoterol-treated rats exhibited a 13% increase in fiber CSA and a 17% increase in Po above that of clenbuterol-treated rats. These data indicate that fenoterol has greater effects on the functional properties of rat skeletal muscles than clenbuterol.

scholarly journals In vitro acute effects of free fatty acids on protein degradation in young rat skeletal muscle

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Lidiany Góis ◽  
Neusa Maria Zanon ◽  
Renato Helios Migliorini ◽  
Isis do Carmo Kettelhut
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Protein Degradation ◽  
Acute Effects ◽  
Rat Skeletal Muscle ◽  
Young Rat
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