Loss of α-actinin-3 confers protection from eccentric contraction damage in fast-twitch EDL muscles from aged mdx dystrophic mice by reducing pathological fibre branching

2021 ◽  
Author(s):  
Leonit Kiriaev ◽  
Peter J. Houweling ◽  
Kathryn N. North ◽  
Stewart I. Head
Keyword(s):  
Morphological Changes ◽  
Eccentric Contraction ◽  
Muscle Fibres ◽  
Double Knockout ◽  
Reduction In Force ◽  
The Common ◽  
Fast Twitch ◽  
Skeletal Muscle Fibres ◽  
Dystrophic Mice

ABSTRACTThe common null polymorphism (R577X) in the ACTN3 gene is present in over 1.5 billion people worldwide and results in the absence of the protein α-actinin-3 from the Z-discs of fast-twitch skeletal muscle fibres. We have previously reported that this polymorphism is a modifier of dystrophin deficient Duchenne Muscular Dystrophy. To investigate the mechanism underlying this we use a double knockout (dk)Actn3KO/mdx (dKO) mouse model which lacks both dystrophin and sarcomere α-actinin-3. We used dKO mice and mdx dystrophic mice at 12 months (aged) to investigate the correlation between morphological changes to the fast-twitch dKO EDL and the reduction in force deficit produced by an in vitro eccentric contraction protocol. In the aged dKO mouse we found a marked reduction in fibre branching complexity that correlated with protection from eccentric contraction induced force deficit. Complex branches in the aged dKO EDL fibres (28%) were substantially reduced compared to aged mdx EDL fibres (68%) and this correlates with a graded force loss over three eccentric contractions for dKO muscles (∼35% after first contraction, ∼66% overall) compared to an abrupt drop in mdx upon the first eccentric contraction (∼73% after first contraction, ∼89% after three contractions). In dKO protection from eccentric contraction damage was linked with a doubling of SERCA1 pump density the EDL. We propose that the increased oxidative metabolism of fast-twitch glycolytic fibres characteristic of the null polymorphism (R577X) and increase in SR Ca2+ pump proteins reduces muscle fibre branching and decreases susceptibility to eccentric injury in the dystrophinopathies.

scholarly journals The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Christina Simon ◽  
Almuth Einspanier
Keyword(s):  
Morphological Changes ◽  
Common Marmoset ◽  
Cervical Ripening ◽  
Cervical Tissue ◽  
Ecm Remodeling ◽  
Marmoset Monkey ◽  
Gene And Protein Expression ◽  
The Common

Controversy still exists regarding the involvement of relaxin (RLX) in cervical reorganization throughout parturition in the human, despite its well-known role in facilitating extensive extracellular matrix (ECM) remodeling in diverse organs. Therefore, the aim of the present study was to examine the influence of RLX and estrogen (E2) on the cervical tissue of the common marmoset monkey. Two experimental designs were used: 1)in vivoanalysis of the intracervical diameter under locally applied RLX and 2) ovariectomized (ov) marmosets were treated systemically with either recombinant human (rh) RLX, E2 or rhRLX+E2 to examine their action on the cervix.In vivo-locally applied rhRLX induced a distinct and significant widening of the cervix (before: 4.8±1.1 mm versus after: 5.7±0.9 mm in diameter;P<0.030, MV±s.e.m.). This widening effect was most pronounced in animals without previous pregnancies.In vitroinvestigation of cervical tissue showed significantly increased wet weights after all three hormone treatments (E2: 0.27±0.07 g, RLX: 0.25±0.04 g, E2+RLX: 0.30±0.11 g; allP<0.05; MV±s.e.m.) versus controls (0.10±0.04 g). Furthermore, morphological changes such as loosening of the connective tissue structure and decline in collagen content, an increase in the number of eosinophils, increased the expression of matrix metalloproteinases (MMP1) and MMP2, as well as gene and protein expression of the RLX receptor RXFP1 could be detected in the cervical tissue after all hormone treatments, compared with controls. In summary, RLX has a potent widening effect on the cervix of the common marmoset monkey. Although E2 is not required for this RLX effect, a combined application of E2 and RLX induced the most prominent cervical ripening.

Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols

2001 ◽  
Vol 91 (3) ◽  
pp. 1237-1244 ◽  
Author(s):  
Rune Aslesen ◽  
Ellen M. L. Engebretsen ◽  
Jesper Franch ◽  
Jørgen Jensen
Keyword(s):  
Glucose Uptake ◽  
Wistar Rats ◽  
Metabolic Stress ◽  
Reduction In Force ◽  
Tracer Amount ◽  
Slow Twitch ◽  
Fast Twitch ◽  
The Relationship ◽  
Glycogen Breakdown

In the present study, the relationship between the pattern of electrical stimulation and glucose uptake was investigated in slow-twitch muscles (soleus) and fast-twitch muscles (epitrochlearis) from Wistar rats. Muscles were stimulated electrically for 30 min in vitro with either single pulses (frequencies varied between 0.8 and 15 Hz) or with 200-ms trains (0.1–2 Hz). Glucose uptake (measured with tracer amount of 2-[3H]deoxyglucose) increased with increasing number of impulses whether delivered as single pulses or as short trains. The highest glucose uptake achieved with short tetanic contractions was similar in soleus and epitrochlearis (10.9 ± 0.7 and 12.0 ± 0.8 mmol · kg dry wt−1 · 30 min−1, respectively). Single pulses, on the other hand, increased contraction-stimulated glucose uptake less in soleus than in epitrochlearis (7.5 ± 1.1 and 11.7 ± 0.5 mmol · kg dry wt−1 · 30 min−1, respectively; P < 0.02). Glucose uptake correlated with glycogen breakdown in soleus ( r = 0.84, P < 0.0001) and (epitrochlearis: r = 0.91, P < 0.0001). Contraction-stimulated glucose uptake also correlated with breakdown of ATP and PCr and with reduction in force. Our data suggest that metabolic stress mediates contraction-stimulated glucose uptake.

The effect of ionic strength on the kinetics of rigor development in skinned fast-twitch skeletal muscle fibres

1998 ◽  
Vol 435 (6) ◽  
pp. 753-761 ◽  
Author(s):  
C. Veigel ◽  
R. D. von Maydell ◽  
K.R. Kress ◽  
J. E. Molloy ◽  
R. H. A. Fink
Keyword(s):  
Skeletal Muscle ◽  
Ionic Strength ◽  
Muscle Fibres ◽  
Fast Twitch ◽  
Skeletal Muscle Fibres ◽  
Kinetics Of

Succinic dehydrogenase activity of forelimb and hindlimb muscles of the dystrophic mouse

1984 ◽  
Vol 62 (8) ◽  
pp. 905-911 ◽  
Author(s):  
D. J. Parry ◽  
G. Desypris
Keyword(s):  
Enzyme Activity ◽  
Succinic Dehydrogenase ◽  
Muscle Fibres ◽  
Image Analyzer ◽  
Dystrophic Muscle ◽  
Hindlimb Muscles ◽  
Fast Twitch ◽  
Whole Muscle ◽  
Histochemical Changes ◽  
Dystrophic Mice

The activity of succinic dehydrogenase (SDH) was determined in muscles of normal and dystrophic mice. In contradistinction to reports based solely upon histochemical examination, we were unable to observe increased activity in fast-twitch muscles of dystrophic mice. Because dystrophic muscles contain large amounts of connective tissue, two reference bases for expression of enzyme activity were compared. SDH activity was expressed either per micromole of creatine or per milligram of "true muscle fibre weight." The latter was obtained by determining the proportion of the whole muscle occupied by muscle fibres using an image analyzer with photographs of muscle cross section. It appears that the use of creatine content as an index of muscle mass may not be valid for pathological tissue, as the concentration of creatine in some dystrophic muscles differed from that of control muscles. Hindlimb muscles of dystrophic mice exhibit continuous spontaneous activity. To determine the effects of this on oxidative enzyme activity two fast-twitch muscles from the forelimb were also examined. Although they showed histochemical changes comparable to those seen in hindlimb muscles, there was no increase in SDH activity. The only dystrophic muscle examined which showed a change in SDH activity was the soleus in which a decrease was observed.

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