Moderate and high intensity sprint exercise induce differential responses in<i>COX4I2</i>and<i>PDK4</i>gene expression in Thoroughbred horse skeletal muscle

Hill, E. W.; Eivers, Suzanne S.; McGivney, Beatrice A.; Fonseca, R.; Gu, Jingjing; Smith, N.; Browne, John A.; MacHugh, David E.; Katz, Lisa

doi:10.1111/j.2042-3306.2010.00206.x

Cited by 23 publications

(18 citation statements)

References 29 publications

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“…With the potential role in hypoxic metabolism, several researchers have asked if COX4-2 has a greater role in comparative models that may experience functional or environmental hypoxia, including high-performance thoroughbred horses and high-altitude specialist pikas; however, no evidence for a greater role of COX4-2 was found (Luo et al 2008;Eivers et al 2010;Hill et al 2010). Thus, although COX4 paralogs appear to confer functional differences on the COX complex and appear to be differentially regulated by oxygen in some species, the extent of their role in the hypoxic response has yet to be elucidated.…”

Section: Hypoxia and Cox4 Structure And Gene Expressionmentioning

confidence: 96%

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Bremer

SniderT.

2014

Can. J. Zool.

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Modification of mitochondrial content demands the synthesis of hundreds of proteins encoded by nuclear and mitochondrial genomes. The responsibility for coordination of this process falls to nuclear-encoded master regulators of transcription. DNAbinding proteins and coactivators integrate information from energy-sensing pathways and hormones to alter mitochondrial gene expression. In mammals, the signaling cascade for mitochondrial biogenesis can be described as follows: hormonal signals and energetic information are sensed by protein-modifying enzymes that in turn regulate the post-translational modification of transcription factors. Once activated, transcription-factor complexes form on promoter elements of many of the nuclear-encoded mitochondrial genes, recruiting proteins that remodel chromatin and initiate transcription. One master regulator in mammals, PGC-1␣, is well studied because of its role in determining the metabolic phenotype of muscles, but also due to its importance in mitochondria-related metabolic diseases. However, relatively little is known about the role of this pathway in other vertebrates. These uncertainties raise broader questions about the evolutionary origins of the pathway and its role in generating the diversity in muscle metabolic phenotypes seen in nature.Résumé : La modification du contenu mitochondrial nécessite la synthèse de centaines de protéines encodées par les génomes nucléaire et mitochondrial, la coordination de ce processus étant assurée par des maîtres régulateurs de la transcription codés par le génome nucléaire. Des protéines se liant à l'ADN et des coactivateurs intègrent l'information provenant de voies de détection de l'énergie et d'hormones pour ensuite modifier l'expression des gènes mitochondriaux. Chez les mammifères, la cascade de signalisation pour la biogénèse mitochondriale peut être décrite comme suit : des enzymes de modification de protéines détectent des signaux hormonaux et de l'information énergétique et régulent la modification post-traduction des facteurs de transcription. Une fois activés, des complexes de facteurs de transcription se forment sur des éléments promoteurs de nombreux gènes mitochondriaux à encodage nucléaire, recrutant des protéines qui remodèlent la chromatine et amorcent la transcription. Un des maîtres régulateurs chez les mammifères, le PGC-1␣, fait l'objet de nombreuses études en raison de son rôle dans la détermination du phénotype métabolique des muscles, mais aussi en raison de son importance dans les maladies métaboliques associées aux mitochondries. Les connaissances sur le rôle de cette voie chez d'autres vertébrés sont toutefois limitées. Ces incertitudes soulèvent des questions plus larges concernant les origines évolutives de cette voie et son rôle dans la production de la diversité de phénotypes métaboliques musculaires observée dans la nature. [Traduit par la Rédaction]

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Section: Hypoxia and Cox4 Structure And Gene Expressionmentioning

confidence: 96%

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Bremer

SniderT.

2014

Can. J. Zool.

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“…As the PDK4 is involved with physical exercise through energy production, polymorphisms in this gene have been successfully associated with performance traits in horses. In Thoroughbred racehorses, the SNP g.38973231A>G was strongly associated with racing performance (Hill et al 2010). In this study, individuals of AA and AG genotype performed better than the GG genotype.…”

Section: Candidate Genes For Performancementioning

confidence: 59%

“…Two candidate genes, PDK4 and DMRT3, have been studied for athletic potential as possible markers for performance in horses. The expression of the pyruvate dehydrogenase kinase, isozyme 4 -PDK4 (Gu et al 2009, Hill et al 2010, located on equine chromosome 4 (ECA4) helps to control metabolism and glucose conversion to acetyl-CoA for production of ATP (Andrews et al 1998). This regulation of glucose conversion is tightly controlled by conversion of pyruvate to acetyl-CoA in the mitochondrion by catalytic function of the pyruvate dehydrogenase complex (PDC), which is controlled by pyruvate dehydrogenase kinase (PDK).…”

Section: Candidate Genes For Performancementioning

confidence: 99%

Candidate genes for performance in horses, including monocarboxylate transporters

et al. 2017

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Some horse breeds are highly selected for athletic activities. The athletic potential of each animal can be measured by its performance in sports. High athletic performance depends on the animal capacity to produce energy through aerobic and anaerobic metabolic pathways, among other factors. Transmembrane proteins called monocarboxylate transporters, mainly the isoform 1 (MCT1) and its ancillary protein CD147, can help the organism to adapt to physiological stress caused by physical exercise, transporting lactate and H+ ions. Horse breeds are selected for different purposes so we might expect differences in the amount of those proteins and in the genotypic frequencies for genes that play a significant role in the performance of the animals. The study of MCT1 and CD147 gene polymorphisms, which can affect the formation of the proteins and transport of lactate and H+, can provide enough information to be used for selection of athletic horses increasingly resistant to intense exercise. Two other candidate genes, the PDK4 and DMRT3, have been associated with athletic potential and indicated as possible markers for performance in horses. The oxidation of fatty acids is highly effective in generating ATP and is controlled by the expression of PDK4 (pyruvate dehydrogenase kinase, isozyme 4) in skeletal muscle during and after exercise. The doublesex and mab-3 related transcription factor 3 (DMRT3) gene encodes an important transcription factor in the setting of spinal cord circuits controlling movement in vertebrates and may be associated with gait performance in horses. This review describes how the monocarboxylate transporters work during physical exercise in athletic horses and the influence of polymorphisms in candidate genes for athletic performance in horses.

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“…The complex is negatively regulated by PDK4 , resulting in decreased glucose oxidation concomitant with increased fatty acid oxidation (Hill et al . ). A link was found between the PDK4 marker and elite racing performance in thoroughbreds, suggesting that this gene plays a key role in regulating strenuous exercise (Hill et al .…”

Section: Discussionmentioning

confidence: 97%

Quantitative analysis of short‐ and long‐distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses

Rama

Valera

Membrillo

et al. 2016

J Animal Breeding Genetics

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The association of five candidate genes with sporting performance in young and adult Spanish Trotter horses (STHs) was performed according to a previous selection based on quantitative analysis of the trait time per kilometre (TPK). A total of 334 516 records of TPK from 5958 STHs were used to estimate the estimated breeding values (EBVs) at different age groups (young and adults horses) throughout the range of distances (1600-2700 m) using a bicharacter random regression model. The heritability estimated by distance ranged from 0.16 to 0.40, with a different range for the two age groups. Considering the animals with the best and the worst deregressed EBV, 321 STHs were selected for SNP genotyping in MSTN, COX4I2, PDK4, DMRT3 and CKM genes. An association analysis based on ridge and logistic regression revealed that the young trotters with genotype GG in PDK4 (p < 0.05) and AA of DMRT3 (p < 0.001) SNPs show the best potential in short-distance races, while those carrying the genotype AA in DMRT3 (p < 0.001) and CC in CKM (p < 0.05) genes seem to be the best in long-distance races. Adult trotters with genotype AA in DMRT3 also display greater speed (p < 0.05) and endurance (p < 0.001).

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Moderate and high intensity sprint exercise induce differential responses inCOX4I2andPDK4gene expression in Thoroughbred horse skeletal muscle

Abstract: Different exercise protocols elicit variable transcriptional responses in key exercise relevant genes in equine skeletal muscle due to variation in metabolic demand.

Cited by 23 publications

References 29 publications

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Candidate genes for performance in horses, including monocarboxylate transporters

Quantitative analysis of short‐ and long‐distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses

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