Phosphorylation of skeletal muscle contractile proteins in vivo

Barth syndrome is a rare and incurable X-linked (male-specific) genetic disease that affects the protein tafazzin (Taz). Taz is an important enzyme responsible for synthesizing biologically relevant cardiolipin (for heart and skeletal muscle, cardiolipin rich in linoleic acid), a critical phospholipid of mitochondrial form and function. Mutations to Taz cause dysfunctional mitochondria, resulting in exercise intolerance due to skeletal muscle weakness. To date, there has been limited research on improving skeletal muscle function, with interventions focused on endurance and resistance exercise. Previous cell culture research has shown therapeutic potential for the addition of exogenous linoleic acid in improving Taz-deficient mitochondrial function but has not been examined in vivo. The purpose of this study was to examine the influence of supplemental dietary linoleic acid on skeletal muscle function in a rodent model of Barth syndrome, the inducible Taz knockdown (TazKD) mouse. One of the main findings was that TazKD soleus demonstrated an impaired contractile phenotype (slower force development and rates of relaxation) in vitro compared to their WT littermates. Interestingly, this impaired contractile phenotype seen in vitro did not translate to altered muscle function in vivo at the whole-body level. Also, supplemental linoleic acid attenuated, to some degree, in vitro impaired contractile phenotype in TazKD soleus, and these findings appear to be partially mediated by improvements in cardiolipin content and resulting mitochondrial supercomplex formation. Future research will further examine alternative mechanisms of dietary supplemental LA on improving skeletal muscle contractile dysfunction in TazKD mice.

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cDNA clone analysis of six co-regulated mRNAs encoding skeletal muscle contractile proteins.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.79.5.1553 ◽

1982 ◽

Vol 79 (5) ◽

pp. 1553-1557 ◽

Cited By ~ 62

Author(s):

K. E. Hastings ◽

C. P. Emerson

Keyword(s):

Skeletal Muscle ◽

Cdna Clone ◽

Contractile Proteins ◽

Clone Analysis ◽

Muscle Contractile

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Turnover of skeletal muscle contractile proteins in glucocorticoid myopathy

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/0960-0760(94)90165-1 ◽

1994 ◽

Vol 50 (1-2) ◽

pp. 1-4 ◽

Cited By ~ 30

Author(s):

Teet Seene

Keyword(s):

Skeletal Muscle ◽

Contractile Proteins ◽

Muscle Contractile

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The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different mouse chromosomes.

The EMBO Journal ◽

10.1002/j.1460-2075.1982.tb01314.x ◽

1982 ◽

Vol 1 (11) ◽

pp. 1299-1305 ◽

Cited By ~ 43

Author(s):

H. Czosnek ◽

U. Nudel ◽

M. Shani ◽

P.E. Barker ◽

D.D. Pravtcheva ◽

...

Keyword(s):

Skeletal Muscle ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Light Chain ◽

Myosin Light Chain ◽

Contractile Proteins ◽

Muscle Actin ◽

Myosin Light Chain 2 ◽

Muscle Contractile

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Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

PLoS ONE ◽

10.1371/journal.pone.0249472 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249472

Author(s):

Pangdra Vang ◽

Cory W. Baumann ◽

Rebecca Barok ◽

Alexie A. Larson ◽

Brendan J. Dougherty ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Strength ◽

Contractile Function ◽

Estrogen Deficiency ◽

Diaphragm Muscle ◽

Whole Body ◽

Ventilatory Function ◽

Fourth Decade ◽

Muscle Contractile

Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury.

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Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00370.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. E145-E151 ◽

Cited By ~ 3

Author(s):

Kristoffer Svensson ◽

Shahriar Tahvilian ◽

Vitor F. Martins ◽

Jessica R. Dent ◽

Adrianna Lemanek ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Homeostasis ◽

Mitochondrial Biogenesis ◽

Exercise Performance ◽

Wheel Running ◽

Contractile Function ◽

Muscle Contractile ◽

Combined Overexpression ◽

Voluntary Wheel

Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) acetylation status and activity. However, the combined contribution of SIRT1 and GCN5 to skeletal muscle metabolism and endurance performance in vivo is unknown. In this study, we investigated the impact of combined skeletal muscle-specific overexpression of SIRT1 and deletion of GCN5 on glucose homeostasis, skeletal muscle mitochondrial biogenesis and function, and metabolic adaptation to endurance exercise training in mice. We generated mice with combined and tamoxifen-inducible skeletal muscle-specific overexpression of SIRT1 and knockout of GCN5 (dTG) and floxed [wild type (WT)] littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5–6 wk of age, and 4–7 wk later glucose homeostasis, skeletal muscle contractile function, mitochondrial function, and the effects of 14 days of voluntary wheel running on expression of metabolic proteins and exercise capacity were assessed. There was no difference in oral glucose tolerance, skeletal muscle contractile function, mitochondrial abundance, or maximal respiratory capacity between dTG and WT mice. Additionally, there were no genotype differences in exercise performance and markers of mitochondrial biogenesis after 14 days of voluntary wheel running. These results demonstrate that combined overexpression of SIRT1 and loss of GCN5 in vivo does not promote metabolic remodeling in skeletal muscle of sedentary or exercise-trained mice.

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