Wild antelope skeletal muscle antioxidant enzyme activities do not correlate with muscle fibre type or oxidative metabolism

AbstractHorse racing is a popular and financially important industry worldwide and researchers and horse owners are interested in genetic and training influences that maximise athletic performance. An association has been found between the presence of a short interspersed nuclear element (SINE) mutation in the myostatin (MSTN) gene promoter and optimal race distance in Thoroughbred horses. There is previous laboratory evidence that this mutation reduces MSTN expression in a cell culture model and influences skeletal muscle fibre type proportions in horses. Manipulating MSTN expression has been proposed for illicit gene doping in human and equine athletes and already, researchers have generated homozygous and heterozygous MSTN-null horse embryos following CRISPR/Cas9 editing at the equine MSTN locus and nuclear transfer, aiming artificially to enhance performance. To date however, the role of the naturally-occurring equine MSTN SINE mutation in vivo has remained unclear; here we hypothesised that it reduces, but does not ablate circulating myostatin expression. Following validation of an ELISA for detection of myostatin in equine serum and using residual whole blood and serum samples from 176 Thoroughbred racehorses under identical management, horses were genotyped for the SINE mutation by PCR and their serum myostatin concentrations measured. In our population, the proportions of SINE homozygotes, heterozygotes and normal horses were 27%, 46% and 27% respectively. Results indicated that horses that are homozygous for the SINE mutation have detectable, but significantly lower (p < 0.0001) serum myostatin concentrations (226.8 pg/ml; 69.3–895.4 pg/ml; median; minimum–maximum) than heterozygous (766 pg/ml; 64.6–1182 pg/ml) and normal horses (1099 pg/ml; 187.8–1743 pg/ml). Heterozygotes have significantly lower (p < 0.0001) myostatin concentrations than normal horses. Variation in serum myostatin concentrations across horses was not influenced by age or sex. This is the first study to reveal the direct functional effect of a highly prevalent mutation in the equine MSTN gene associated with exercise performance. Determining the reason for variation in expression of myostatin within SINE-genotyped groups might identify additional performance-associated environmental or genetic influences in Thoroughbreds. Understanding the mechanism by which altered myostatin expression influences skeletal muscle fibre type remains to be determined.

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Skeletal muscle fibre type and capillary density in college-aged blacks and whites

Annals of Human Biology ◽

10.1080/03014469700005072 ◽

1997 ◽

Vol 24 (4) ◽

pp. 323-331 ◽

Cited By ~ 25

Author(s):

W.J. Duey ◽

D.R. Bassett ◽

D.J. Torok ◽

E.T. Howley ◽

V. Bond ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Fibre ◽

Fibre Type ◽

Skeletal Muscle Fibre ◽

Capillary Density ◽

Muscle Fibre Type ◽

Blacks And Whites

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Decreased Mitochondrial Oxygen Consumption and Antioxidant Enzyme Activities in Skeletal Muscle of Dystrophic Mice after Low-Intensity Exercise

Annals of Nutrition and Metabolism ◽

10.1159/000046707 ◽

2001 ◽

Vol 45 (2) ◽

pp. 58-66 ◽

Cited By ~ 20

Author(s):

V. Faist ◽

J. König ◽

H. Höger ◽

I. Elmadfa

Keyword(s):

Skeletal Muscle ◽

Oxygen Consumption ◽

Antioxidant Enzyme ◽

Enzyme Activities ◽

Antioxidant Enzyme Activities ◽

Mitochondrial Oxygen Consumption ◽

Low Intensity ◽

Low Intensity Exercise ◽

Dystrophic Mice

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Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.267.2.r439 ◽

1994 ◽

Vol 267 (2) ◽

pp. R439-R445 ◽

Cited By ~ 38

Author(s):

C. Leeuwenburgh ◽

R. Fiebig ◽

R. Chandwaney ◽

L. L. Ji

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Antioxidant Enzyme ◽

Enzyme Activities ◽

Vastus Lateralis ◽

Antioxidant Systems ◽

Antioxidant Enzyme Activities ◽

Vastus Lateralis Muscle ◽

Adult Rats ◽

Young Rats

Glutathione (GSH) content and antioxidant enzyme activities were investigated in skeletal muscle of young, adult, and old male Fischer 344 rats. Furthermore, the effect of 10 wk of exercise training on these antioxidant systems was evaluated at all ages. In the soleus muscle, GSH concentration increased markedly with age, with no significant change in glutathione disulfide (GSSG) content. Training caused a 30% decrease of GSH (P < 0.05) in the soleus of young rats and a reduction of the GSH-to-GSSG ratio at all ages. Activity of gamma-glutamyl transpeptidase (GGT), a key enzyme for GSH uptake by muscle, was also significantly decreased with training. GSH, GSSG, and the GSH-to-GSSG ratio were not altered with aging or training in the deep portion of vastus lateralis muscle (DVL). Activities of GSH peroxidase (GPX), GSSG reductase (GR), superoxide dismutase (SOD), catalase (CAT), and GSH sulfur-transferase were increased significantly with aging in both soleus and DVL. In DVL, training increased GPX and SOD activities in the young rats, whereas in soleus, training decreased GR and CAT activities in the adult rats and GGT and CAT activities in the old rats. Muscle lipid peroxidation was significantly increased with aging in both DVL and soleus but was not affected by training. These data indicate that aging may cause not only an overall elevation of antioxidant enzyme activities but also a fiber-specific adaptation of GSH system in skeletal muscle. Exercise training, although increasing selective antioxidant enzymes in the young rats, does not offer additional protection against oxidative stress in the senescent muscle.

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A Highly Prevalent SINE Mutation in The Myostatin (MSTN) Gene Promoter Is Associated With Low Circulating Myostatin Concentration in Thoroughbred Racehorses

10.21203/rs.3.rs-149900/v1 ◽

2021 ◽

Author(s):

Victoria O'Hara ◽

Amelie Cowan ◽

Dominique Riddell ◽

Claire Massey ◽

John Martin ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Fibre ◽

Fibre Type ◽

Skeletal Muscle Fibre ◽

Gene Promoter ◽

Muscle Fibre Type ◽

Serum Samples ◽

Thoroughbred Racehorses ◽

A Cell

Abstract Horse racing is a popular and financially important industry worldwide and researchers and horse owners are interested in genetic and training influences that maximise athletic performance. An association has been found between the presence of a short interspersed nuclear element (SINE) mutation in the myostatin (MSTN) gene promoter and optimal race distance in Thoroughbred horses. There is previous laboratory evidence that this mutation reduces MSTN expression in a cell culture model and influences skeletal muscle fibre type proportions in horses. Manipulating MSTN expression has been proposed for illicit gene doping in human and equine athletes and already, researchers have generated homozygous and heterozygous MSTN-null horse embryos following CRISPR/Cas9 editing at the equine MSTN locus and nuclear transfer, aiming artificially to enhance performance. To date however, the role of the naturally-occurring equine MSTN SINE mutation in vivo has remained unclear; here we hypothesised that it reduces, but does not ablate circulating myostatin expression. Following validation of an ELISA for detection of myostatin in equine serum and using residual whole blood and serum samples from 176 Thoroughbred racehorses under identical management, horses were genotyped for the SINE mutation by PCR and their serum myostatin concentrations measured. In our population, the proportions of SINE homozygotes, heterozygotes and normal horses were 27%, 46% and 27% respectively. Results indicated that horses that are homozygous for the SINE mutation have detectable, but significantly lower (p<0.0001) serum myostatin concentrations (226.8pg/ml; 69.3-895.4pg/ml; median; minimum-maximum) than heterozygous (766pg/ml; 64.6-1182pg/ml) and normal horses (1099pg/ml; 187.8-1743pg/ml). Heterozygotes have significantly lower (p<0.0001) myostatin concentrations than normal horses. Variation in serum myostatin concentrations across horses was not influenced by age or sex. This is the first study to reveal the direct functional effect of a highly prevalent mutation in the equine MSTN gene associated with exercise performance. Determining the reason for variation in expression of myostatin within SINE-genotyped groups might identify additional performance-associated environmental or genetic influences in Thoroughbreds. Understanding the mechanism by which altered myostatin expression influences skeletal muscle fibre type remains to be determined.

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