Intracellular effect of β3-adrenoceptor agonist Carazolol on skeletal muscle, a direct interaction with SERCA

Cell Calcium ◽  
2019 ◽  
Vol 79 ◽  
pp. 20-26 ◽  
Author(s):  
Ibrahim Ramirez-Soto ◽  
Eduardo Rodriguez ◽  
Rocío Alvarez ◽  
Eugenio Quiroz ◽  
Alicia Ortega
Keyword(s):  
Skeletal Muscle ◽  
Direct Interaction ◽  
Intracellular Effect ◽  
Adrenoceptor Agonist

scholarly journals Intracellular Effect of β3-Adrenoceptor agonist Carazolol on Skeletal Muscle, a Direct Interaction with SERCA

2018 ◽  
Vol 114 (3) ◽  
pp. 235a
Author(s):  
Ibrahim A. Ramirez ◽  
Eduardo Rodriquez ◽  
Rocío Alvarez ◽  
Eugenio Quiroz ◽  
Alicia Ortega
Keyword(s):  
Skeletal Muscle ◽  
Direct Interaction ◽  
Intracellular Effect ◽  
Adrenoceptor Agonist

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 Altered skeletal muscle microtubule-mitochondrial VDAC2 binding is related to bioenergetic impairments after paclitaxel but not vinblastine chemotherapies

2019 ◽  
Vol 316 (3) ◽  
pp. C449-C455 ◽  
Author(s):  
Sofhia V. Ramos ◽  
Meghan C. Hughes ◽  
Christopher G. R. Perry
Keyword(s):  
Skeletal Muscle ◽  
Direct Interaction ◽  
Permeability Transition Pore ◽  
Anion Channel ◽  
Permeability Transition ◽  
Mitochondrial Bioenergetics ◽  
Voltage Dependent Anion Channel ◽  
Retention Capacity ◽  
Microtubule Stabilization

Microtubule-targeting chemotherapies are linked to impaired cellular metabolism, which may contribute to skeletal muscle dysfunction. However, the mechanisms by which metabolic homeostasis is perturbed remains unknown. Tubulin, the fundamental unit of microtubules, has been implicated in the regulation of mitochondrial-cytosolic ADP/ATP exchange through its interaction with the outer membrane voltage-dependent anion channel (VDAC). Based on this model, we predicted that disrupting microtubule architecture with the stabilizer paclitaxel and destabilizer vinblastine would impair skeletal muscle mitochondrial bioenergetics. Here, we provide in vitro evidence of a direct interaction between both α-tubulin and βII-tubulin with VDAC2 in untreated single extensor digitorum longus (EDL) fibers. Paclitaxel increased both α- and βII-tubulin-VDAC2 interactions, whereas vinblastine had no effect. Utilizing a permeabilized muscle fiber bundle preparation that retains the cytoskeleton, paclitaxel treatment impaired the ability of ADP to attenuate H2O2 emission, resulting in greater H2O2 emission kinetics. Despite no effect on tubulin-VDAC2 binding, vinblastine still altered mitochondrial bioenergetics through a surprising increase in ADP-stimulated respiration while also impairing ADP suppression of H2O2 and increasing mitochondrial susceptibility to calcium-induced formation of the proapoptotic permeability transition pore. Collectively, these results demonstrate that altering microtubule architecture with chemotherapeutics disrupts mitochondrial bioenergetics in EDL skeletal muscle. Specifically, microtubule stabilization increases H2O2 emission by impairing ADP sensitivity in association with greater tubulin-VDAC binding. In contrast, decreasing microtubule abundance triggers a broad impairment of ADP’s governance of respiration and H2O2 emission as well as calcium retention capacity, albeit through an unknown mechanism.

scholarly journals Direct Interaction between Myocyte Enhancer Factor 2 (MEF2) and Protein Phosphatase 1α Represses MEF2-Dependent Gene Expression

2009 ◽  
Vol 29 (12) ◽  
pp. 3355-3366 ◽  
Author(s):  
R. L. S. Perry ◽  
C. Yang ◽  
N. Soora ◽  
J. Salma ◽  
M. Marback ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Protein Interactions ◽  
Protein Phosphatase ◽  
Hippocampal Neurons ◽  
Neuronal Cell ◽  
Direct Interaction ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

ABSTRACT The myocyte enhancer factor 2 (MEF2) transcription factors play important roles in neuronal, cardiac, and skeletal muscle tissues. MEF2 serves as a nuclear sensor, integrating signals from several signaling cascades through protein-protein interactions with kinases, chromatin remodeling factors, and other transcriptional regulators. Here, we report a novel interaction between the catalytic subunit of protein phosphatase 1α (PP1α) and MEF2. Interaction occurs within the nucleus, and binding of PP1α to MEF2 potently represses MEF2-dependent transcription. The interaction utilizes uncharacterized domains in both PP1α and MEF2, and PP1α phosphatase activity is not obligatory for MEF2 repression. Moreover, a MEF2-PP1α regulatory complex leads to nuclear retention and recruitment of histone deacetylase 4 to MEF2 transcription complexes. PP1α-mediated repression of MEF2 overrides the positive influence of calcineurin signaling, suggesting PP1α exerts a dominant level of control over MEF2 function. Indeed, PP1α-mediated repression of MEF2 function interferes with the prosurvival effect of MEF2 in primary hippocampal neurons. The PP1α-MEF2 interaction constitutes a potent locus of control for MEF2-dependent gene expression, having potentially important implications for neuronal cell survival, cardiac remodeling in disease, and terminal differentiation of vascular, cardiac, and skeletal muscle.

STIM1 negatively regulates Ca2+ release from the sarcoplasmic reticulum in skeletal myotubes

2013 ◽  
Vol 453 (2) ◽  
pp. 187-200 ◽  
Author(s):  
Keon Jin Lee ◽  
Jin Seok Woo ◽  
Ji-Hye Hwang ◽  
Changdo Hyun ◽  
Chung-Hyun Cho ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Direct Interaction ◽  
Dominant Negative ◽  
Wild Type ◽  
Triple Mutant ◽  
Direct Role ◽  
Independent Manner ◽  
C Terminus ◽  
The Times

STIM1 (stromal interaction molecule 1) mediates SOCE (store-operated Ca2+ entry) in skeletal muscle. However, the direct role(s) of STIM1 in skeletal muscle, such as Ca2+ release from the SR (sarcoplasmic reticulum) for muscle contraction, have not been identified. The times required for the maximal expression of endogenous STIM1 or Orai1, or for the appearance of puncta during the differentiation of mouse primary skeletal myoblasts to myotubes, were all different, and the formation of puncta was detected with no stimulus during differentiation, suggesting that, in skeletal muscle, the formation of puncta is a part of the differentiation. Wild-type STIM1 and two STIM1 mutants (Triple mutant, missing Ca2+-sensing residues but possessing the intact C-terminus; and E136X, missing the C-terminus) were overexpressed in the myotubes. The wild-type STIM1 increased SOCE, whereas neither mutant had an effect on SOCE. It was interesting that increases in the formation of puncta were observed in the Triple mutant as well as in wild-type STIM1, suggesting that SOCE-irrelevant puncta could exist in skeletal muscle. On the other hand, overexpression of wild-type or Triple mutant, but not E136X, attenuated Ca2+ releases from the SR in response to KCl [evoking ECC (excitation–contraction coupling) via activating DHPR (dihydropyridine receptor)] in a dominant-negative manner. The attenuation was removed by STIM1 knockdown, and STIM1 was co-immunoprecipitated with DHRP in a Ca2+-independent manner. These results suggest that STIM1 negatively regulates Ca2+ release from the SR through the direct interaction of the STIM1 C-terminus with DHPR, and that STIM1 is involved in both ECC and SOCE in skeletal muscle.

scholarly journals Presence of enolase in the M-band of skeletal muscle and possible indirect interaction with the cytosolic muscle isoform of creatine kinase

1999 ◽  
Vol 338 (1) ◽  
pp. 115-121 ◽  
Author(s):  
Georges FOUCAULT ◽  
Monique VACHER ◽  
Tatyana MERKULOVA ◽  
Angelica KELLER ◽  
Martine ARRIO-DUPONT
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Energy Metabolism ◽  
Direct Interaction ◽  
Cross Linking ◽  
Muscle Fibres ◽  
Skinned Fibres ◽  
Two Dimensional Gel Electrophoresis ◽  
The Cross ◽  
Skeletal Muscle Fibres

Glycerol-skinned skeletal muscle fibres retain the defined sarcomeric structure of the myofibrils. We show here that a small fraction of two enzymes important for energy metabolism, the cytosolic muscle isoform of creatine kinase (EC 2.7.3.2), MM-creatine kinase (MM-CK), and enolase (EC 4.2.1.11), remains bound to skinned fibres. CK is slowly exchangeable, whereas enolase is firmly bound. Two-dimensional gel electrophoresis followed by Western blot analyses demonstrates that both α (ubiquitous) and β (muscle-specific) subunits of enolase are present in these preparations. Enolase and CK were co-localized at the M-band of the sarcomeres, as observed by indirect immunofluorescence and confocal microscopy. Cross-linking experiments were performed on skinned fibres with three bifunctional succinimidyl esters of different lengths and yielded a protein complex of 150 kDa that reacted with antibodies directed against either M-CK or β-enolase. The cross-linking efficiency was greatest for the longest reagent and zero for the shortest one. The length of the cross-linker giving a covalent complex between the two enzymes does not support the notion of a direct interaction between M-CK and enolase. This is the first demonstration of the presence of an enzyme of energy metabolism other than CK at the M-band of myofibres.

scholarly journals BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via β2-adrenoceptors without causing classical receptor desensitization

2019 ◽  
Vol 316 (5) ◽  
pp. R666-R677 ◽  
Author(s):  
Saori Mukaida ◽  
Masaaki Sato ◽  
Anette I. Öberg ◽  
Nodi Dehvari ◽  
Jessica M. Olsen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Glucose Homeostasis ◽  
Ex Vivo ◽  
Partial Agonist ◽  
Receptor Desensitization ◽  
Glut4 Translocation ◽  
Adrenoceptor Agonist

The type 2 diabetes epidemic makes it important to find insulin-independent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual β2-/β3-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, β2-adrenoceptor desensitization, β-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of β2-adrenoceptors, with a similar potency and efficacy to that of the nonselective β-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit β-arrestin1/2 to the β2-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a β2-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor.

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