scholarly journals Isometric training improves fatigue resistance in dystrophin-deficient muscle

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Nao Yamauchi ◽  
Iori Kimura ◽  
Yuki Ashida ◽  
Azuma Naito ◽  
Nao Tokuda ◽  
...  
Keyword(s):  
Fatigue Resistance ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Blue Dye ◽  
Rich Domain ◽  
Flexor Muscles ◽  
Domain 3 ◽  
Plantar Flexor Muscles ◽  
Cysteine Rich Domain

Eccentric contractions, in which the muscle is stretched during contraction, cause substantially greater damage than isometric (ISO) contractions, in which the length of the muscle does not change during contraction. Here, we tested the hypothesis that ISO training improves fatigue resistance in skeletal muscle from dystrophin-deficient mdx52 mice (15–22 wk old). ISO training (100 Hz stimulation frequency, 0.25-s contractions every 0.5 s, 6 sets of 60 contractions) was performed on the left plantar flexor muscles in vivo with supramaximal electrical stimulation every other day for 4 wk. Compared with the normal control muscle, resistance to fatigue was reduced in the nontrained muscle from mdx52 mice, which was accompanied by a reduction in citrate synthase activity and the LC3BII/I ratio and an increase in the phosphorylation levels of Akt Ser473 and the expression levels of p62. ISO training restored these alterations and markedly increased in vivo fatigue resistance and PGC-1α expression in mdx52 muscles. Moreover, an increased number of Evans Blue dye-positive fibers was significantly reduced by ISO training in mdx52 muscles. In contrast, ISO training did not restore a reduction in the amount of SH3 and cysteine-rich domain 3 in mdx muscles. Thus, our data suggest that mitochondrial function is impaired in dystrophin-deficient muscles, which is likely to be induced by the defective autophagy due to persistent activation of Akt. ISO training inhibits the aberrant activation of Akt presumably by up-regulating the PGC-1α expression, which results in improved mitochondrial function and thus fatigue resistance in dystrophin-deficient muscles.

Preconditioning contractions prevent prolonged force depression and Ca2+-dependent proteolysis of STAC3 after damaging eccentric contractions

2021 ◽  
Author(s):  
Yuki Ashida ◽  
Koichi Himori ◽  
Katsuyuki Tamai ◽  
Iori Kimura ◽  
Takashi Yamada
Keyword(s):  
Medial Gastrocnemius ◽  
Eccentric Contractions ◽  
Blue Dye ◽  
Calpain Inhibitor ◽  
Rich Domain ◽  
Force Depression ◽  
Isometric Torque ◽  
Domain 3 ◽  
Subsequent Activation

Preconditioning contractions (PCs) have been shown to markedly improve recovery from eccentric contractions (ECCs)-induced force depression. We here examined the mechanism behind the effects of PCs with focusing on the SH3 and cysteine rich domain 3 (STAC3) that is essential for coupling membrane depolarization to Ca2+ release from the sarcoplasmic reticulum. Rat medial gastrocnemius (MG) muscles were excised immediately (REC0), 1 day (REC1), and 4 days (REC4) after exposure to 100 repeated damaging ECCs in vivo. PCs with 10 repeated non-damaging ECCs were applied 2 days before the damaging ECCs. Damaging ECCs induced in vivo isometric torque depression at 50 and 100 Hz stimulation frequencies, which was accompanied by a significant decrease in the amount of full-length STAC3, an activation of calpain 1, and an increased number of Evans Blue dye positive fibers in MG muscles at REC1 and REC4. Interestingly, PCs attenuated all these deleterious alterations induced by damaging ECCs. Moreover, mechanistic experiments performed on normal muscle samples exposed to various concentration of Ca2+ showed a Ca2+-dependent proteolysis of STAC3, which was prevented by calpain inhibitor MDL-28170. In conclusion, PCs may improve recovery from force depression after damaging ECCs, in part by inhibiting the loss of STAC3 due to the increased permeability of cell membrane and subsequent activation of calpain 1.

scholarly journals Preconditioning contractions prevent Ca2+-dependent proteolysis of STAC3 and prolonged force depression after eccentric contractions

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Azuma Naito ◽  
Yuki Ashida ◽  
Koichi Himori ◽  
Katsuyuki Tamai ◽  
Iori Kimura ◽  
...  
Keyword(s):  
Medial Gastrocnemius ◽  
Eccentric Contractions ◽  
Blue Dye ◽  
Calpain Inhibitor ◽  
Special Focus ◽  
Rich Domain ◽  
Force Depression ◽  
Domain 3 ◽  
Subsequent Activation

Preconditioning contractions (PCs) have been shown to markedly improve recovery from force depression after damaging eccentric contractions (ECCs). Here, we examined the mechanism underlying the effects of PCs with special focus on the SH3 and cysteine rich domain 3 (STAC3) that is essential for the transduction of action potential to the Ca2+ release from the sarcoplasmic reticulum. Rat medial gastrocnemius (MG) muscles were removed immediately (REC0), 1 d (REC1), and 4 d (REC4) after exposure to 100 repeated in vivo damaging ECCs. PCs with 10 repeated nondamaging ECCs were applied 2 d before the damaging ECCs. Damaging ECCs induced in vivo isometric torque depression at 50 and 100 Hz stimulation frequencies at REC1 and REC4, which was accompanied by a significant reduction in the amount of STAC3, an activation of calpain 1, and an increased number of Evans Blue dye positive fibers in MG muscles. Importantly, PCs attenuated all these deleterious alterations induced by damaging ECCs. Moreover, mechanistic experiments performed on normal muscle tissue exposed to various concentration of Ca2+ showed a Ca2+-dependent proteolysis of STAC3, which was prevented by calpain inhibitor MDL-28170. In conclusion, PCs improve recovery from force depression after damaging ECCs, presumably by inhibiting the loss of STAC3 due to the increased permeability of cell membrane and subsequent activation of calpain 1.

Anaesthesia and neuromuscular disorders: what a neurologist needs to know

2020 ◽  
pp. practneurol-2020-002633
Author(s):  
Luuk R van den Bersselaar ◽  
Marc M J Snoeck ◽  
Madelief Gubbels ◽  
Sheila Riazi ◽  
Erik-Jan Kamsteeg ◽  
...  
Keyword(s):  
General Anaesthesia ◽  
Neuromuscular Disorders ◽  
Muscle Relaxants ◽  
Rich Domain ◽  
Specific Advice ◽  
Voltage Dependent ◽  
Life Threatening ◽  
Ryanodine Receptor 1 ◽  
Domain 3 ◽  
Cysteine Rich Domain

Neurologists are often asked for specific advice regarding patients with neuromuscular disease who require general anaesthesia. However, guidelines on specific neuromuscular disorders do not usually include specific guidelines or pragmatic advice regarding (regional and/or general) anaesthesia or procedural sedation. Furthermore, the medical literature on this subject is mostly limited to publications in anaesthesiology journals. We therefore summarise general recommendations and specific advice for anaesthesia in different neuromuscular disorders to provide a comprehensive and accessible overview of the knowledge on this topic essential for clinical neurologists. A preoperative multidisciplinary approach involving anaesthesiologists, cardiologists, chest physicians, surgeons and neurologists is crucial. Depolarising muscle relaxants (succinylcholine) should be avoided at all times. The dose of non-depolarising muscle relaxants must be reduced and their effect monitored. Patients with specific mutations in RYR1 (ryanodine receptor 1) and less frequently in CACNA1S (calcium channel, voltage-dependent, L type, alpha 1S subunit) and STAC3 (SH3 and cysteine rich domain 3) are at risk of developing a life-threatening malignant hyperthermia reaction.

Chronic effects of muscle and nerve-directed stretching on tissue mechanics

2020 ◽  
Vol 129 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ricardo J. Andrade ◽  
Sandro R. Freitas ◽  
François Hug ◽  
Guillaume Le Sant ◽  
Lilian Lacourpaille ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Tissue Mechanics ◽  
Plantar Flexor ◽  
Chronic Effects ◽  
Flexor Muscles ◽  
Plantar Flexor Muscles

This study demonstrates that the mechanical properties of plantar flexor muscles and sciatic nerve can adapt mechanically to long-term stretching programs. Although interventions targeting muscular or nonmuscular structures are both effective at increasing maximal range of motion, the changes in tissue mechanical properties (stiffness) are specific to the structure being preferentially stretched by each program. We provide the first in vivo evidence that stiffness of peripheral nerves adapts to long-term loading stimuli using appropriate nerve-directed stretching.

scholarly journals Increased Susceptibility of  Thymocytes to Apoptosis in Mice Lacking AIM, a Novel Murine Macrophage-derived Soluble Factor Belonging to the Scavenger Receptor Cysteine-rich Domain Superfamily

1999 ◽  
Vol 189 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Toru Miyazaki ◽  
Yumiko Hirokami ◽  
Nobuyuki Matsuhashi ◽  
Hisakazu Takatsuka ◽  
Makoto Naito
Keyword(s):  
Scavenger Receptor ◽  
The Body ◽  
Murine Macrophage ◽  
Double Positive ◽  
Differential Signal ◽  
Rich Domain ◽  
Macrophage Scavenger Receptor ◽  
Cysteine Rich Domain

Apoptosis of cells must be regulated both positively and negatively in response to a variety of stimuli in the body. Various environmental stresses are known to initiate apoptosis via differential signal transduction cascades. However, induction of signals that may inhibit apoptosis is poorly understood, although a number of intracellular molecules that mediate inhibition of apoptosis have been identified. Here we present a novel murine macrophage-specific 54-kD secreted protein which inhibits apoptosis (termed AIM, for apoptosis inhibitor expressed by macrophages). AIM belongs to the macrophage scavenger receptor cysteine-rich domain superfamily (SRCR-SF), members of which share a highly homologous conserved cysteine-rich domain. In AIM-deficient mice, the thymocyte numbers were diminished to half those in wild-type mice, and CD4/CD8 double-positive (DP) thymocytes were strikingly more susceptible to apoptosis induced by both dexamethasone and irradiation in vivo. Recombinant AIM protein significantly inhibited cell death of DP thymocytes in response to a variety of stimuli in vitro. These results indicate that in the thymus, AIM functions in trans to induce resistance to apoptosis within DP cells, and thus supports the viability of DP thymocytes before thymic selection.

scholarly journals A Single-Amino-Acid Substitution in the TvbS1 Receptor Results in Decreased Susceptibility to Infection by Avian Sarcoma and Leukosis Virus Subgroups B and D and Resistance to Infection by Subgroup E In Vitro and In Vivo

2007 ◽  
Vol 82 (5) ◽  
pp. 2097-2105 ◽  
Author(s):  
Markéta Reinišová ◽  
Filip Šenigl ◽  
Xueqian Yin ◽  
Jiří Plachý ◽  
Josef Geryk ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Genetic Defect ◽  
Single Amino Acid ◽  
Receptor Protein ◽  
Susceptibility To Infection ◽  
Rich Domain ◽  
Domain 3 ◽  
Avian Sarcoma

ABSTRACT The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of ASLV. The tvb gene encodes the receptor for subgroups B, D, and E ASLVs. The wild-type TvbS1 receptor confers susceptibility to subgroups B, D, and E ASLVs. In this study, the genetic defect that accounts for the altered susceptibility of an inbred chicken line, line M, to infection by ASLV(B), ASLV(D), and ASLV(E) was identified. The tvb gene in line M, tvb r2 , encodes a mutant TvbS1 receptor protein with a substitution of a serine for a cysteine at position 125 (C125S). Here, we show that the C125S substitution in TvbS1 significantly reduces the susceptibility of line M cells to infection by ASLV(B) and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in cultured cells and in the incidence and growth of avian sarcoma virus-induced sarcomas in chickens. The C125S substitution significantly reduces the binding affinity of the TvbS1 receptor for the subgroup B, D, and E ASLV envelope glycoproteins. These are the first results that demonstrate a possible role of the cysteine-rich domain 3 in the function of the Tvb receptors.

scholarly journals Citrate Synthase Is a Novel In Vivo Matrix Metalloproteinase-9 Substrate That Regulates Mitochondrial Function in the Postmyocardial Infarction Left Ventricle

2014 ◽  
Vol 21 (14) ◽  
pp. 1974-1985 ◽  
Author(s):  
Lisandra E. de Castro Brás ◽  
Courtney A. Cates ◽  
Kristine Y. DeLeon-Pennell ◽  
Yonggang Ma ◽  
Rugmani Padmanabhan Iyer ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Matrix Metalloproteinase ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Matrix Metalloproteinase 9 ◽  
Postmyocardial Infarction ◽  
Metalloproteinase 9

scholarly journals An Essential Role of the Cysteine-rich Domain of FZD4 in Norrin/Wnt Signaling and Familial Exudative Vitreoretinopathy

2010 ◽  
Vol 286 (12) ◽  
pp. 10210-10215 ◽  
Author(s):  
Kang Zhang ◽  
Yuko Harada ◽  
Xinran Wei ◽  
Dhananjay Shukla ◽  
Anand Rajendran ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Wnt Pathway ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Peripheral Retina ◽  
Familial Exudative Vitreoretinopathy ◽  
Rich Domain ◽  
Cysteine Rich Domain

The Wnt pathway plays important yet diverse roles in health and disease. Mutations in the Wnt receptor FZD4 gene have been confirmed to cause familial exudative vitreoretinopathy (FEVR). FEVR is characterized by incomplete vascularization of the peripheral retina, which can lead to vitreous bleeding, tractional retinal detachment, and blindness. We screened for mutations in the FZD4 gene in five families with FEVR and identified five mutations (C45Y, Y58C, W226X, C204R, and W496X), including three novel mutations (C45Y, Y58C, and W226X). In the retina, Norrin serves as a ligand and binds to FZD4 to activate the Wnt signaling pathway in normal angiogenesis and vascularization. The cysteine-rich domain (CRD) of FZD4 has been shown to play a critical role in Norrin-FZD4 binding. We investigated the effect of mutations in the FZD4 CRD in Norrin binding and signaling in vitro and in vivo. Wild-type and mutant FZD4 proteins were assayed for Norrin binding and Norrin-dependent activation of the canonical Wnt pathway by cell-surface and overlay binding assays and luciferase reporter assays. In HEK293 transfection studies, C45Y, Y58C, and C204R mutants did not bind to Norrin and failed to transduce FZD4-mediated Wnt/β-catenin signaling. In vivo studies using Xenopus embryos showed that these FZD4 mutations disrupt Norrin/β-catenin signaling as evidenced by decreased Siamois and Xnr3 expression. This study identified a new class of FZD4 gene mutations in human disease and demonstrates a critical role of the CRD in Norrin binding and activation of the β-catenin pathway.

scholarly journals Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3

2016 ◽  
Vol 114 (2) ◽  
pp. E228-E236 ◽  
Author(s):  
Jeremy W. Linsley ◽  
I-Uen Hsu ◽  
Linda Groom ◽  
Viktor Yarotskyy ◽  
Manuela Lavorato ◽  
...  
Keyword(s):  
Native American ◽  
Dynamic Imaging ◽  
Release Channel ◽  
Rich Domain ◽  
Dihydropyridine Receptors ◽  
Ec Coupling ◽  
Wide Range ◽  
Ryanodine Receptor 1 ◽  
Domain 3 ◽  
Cysteine Rich Domain

Skeletal muscle contractions are initiated by an increase in Ca2+ released during excitation–contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca2+ release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native American myopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown. Using electron microscopy, electrophysiology, and dynamic imaging of zebrafish muscle fibers, we find significantly reduced DHPR levels, functionality, and stability in stac3 mutants. Furthermore, stac3NAM myofibers exhibited increased caffeine-induced Ca2+ release across a wide range of concentrations in the absence of altered caffeine sensitivity as well as increased Ca2+ in internal stores, which is consistent with increased SR luminal Ca2+. These findings define critical roles for Stac3 in EC coupling and human disease.

Sign in / Sign up

Export Citation Format

Share Document