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  1. Article: Influence of Mechanistic Target of Rapamycin (mTOR)-Regulated Anabolic Pathways on Equine Skeletal Muscle Health.

    Semanchik, Pier L / Wesolowski, Lauren T / Ryan, Patrick J / White-Springer, Sarah H / Fluckey, James D

    Journal of equine veterinary science

    2023  Volume 124, Page(s) 104281

    Abstract: Skeletal muscle is a highly dynamic organ that is essential for locomotion as well as endocrine regulation in all populations of horses. However, despite the importance of adequate muscle development and maintenance, the mechanisms underlying protein ... ...

    Abstract Skeletal muscle is a highly dynamic organ that is essential for locomotion as well as endocrine regulation in all populations of horses. However, despite the importance of adequate muscle development and maintenance, the mechanisms underlying protein anabolism in horses on different diets, exercise programs, and at different life stages remain obscure. Mechanistic target of rapamycin (mTOR) is a key component of the protein synthesis pathway and is regulated by biological factors such as insulin and amino acid availability. Providing a diet ample in vital amino acids, such as leucine and glutamine, is essential in activating sensory pathways that recruit mTOR to the lysosome and assist in the translation of important downstream targets. When the diet is well balanced, mitochondrial biogenesis and protein synthesis are activated in response to increased exercise bouts in the performing athlete. It is important to note that the mTOR kinase pathways are multifaceted and very complex, with several binding partners and targets that lead to specific functions in protein turnover of the cell, and ultimately, the capacity to maintain or grow muscle mass. Further, these pathways are likely altered across the lifespan, with an emphasis of growth in young horses while decreases in musculature with aged horses appears to be attributable to degradation or other regulators of protein synthesis rather than alterations in the mTOR pathway. Previous work has begun to pinpoint ways in which the mTOR pathway is influenced by diet, exercise, and age; however, future research is warranted to quantify the functional outcomes related to changes in mTOR. Promisingly, this could provide direction on appropriate management techniques to support skeletal muscle growth and maximize athletic potential in differing equine populations.
    MeSH term(s) Animals ; Horses ; Signal Transduction/physiology ; Sirolimus/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Muscle, Skeletal/metabolism ; Amino Acids/metabolism
    Chemical Substances Sirolimus (W36ZG6FT64) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Amino Acids
    Language English
    Publishing date 2023-03-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2102631-2
    ISSN 1542-7412 ; 0737-0806
    ISSN (online) 1542-7412
    ISSN 0737-0806
    DOI 10.1016/j.jevs.2023.104281
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  2. Article: Local and systemic responses to repeated gluteal muscle microbiopsies in mature sedentary horses.

    Artman, Jessica L / Wesolowski, Lauren T / Semanchik, Pier L / Isles, JadaLea K / Norton, Sharon A / White-Springer, Sarah H

    Journal of equine veterinary science

    2024  Volume 136, Page(s) 105070

    Abstract: We aimed to test the hypothesis that repeated muscle collections would impact mitochondrial function, antioxidant status, and markers of inflammation and muscle damage. Twenty-six horses (8 geldings, 18 mares; mean ± SD 9.5 ± 3.5 y) had gluteus medius ... ...

    Abstract We aimed to test the hypothesis that repeated muscle collections would impact mitochondrial function, antioxidant status, and markers of inflammation and muscle damage. Twenty-six horses (8 geldings, 18 mares; mean ± SD 9.5 ± 3.5 y) had gluteus medius muscle biopsy samples collected at: 0 and 24h (n=7); 0 and 6h (n = 6); 0, 6, and 12h (n=7); or 0, 6, 12, and 24h (n=6). Blood was collected from all horses every 6h for 72h, starting 24h prior to the 0h muscle collection. Data were analyzed using mixed linear models. Muscle integrative (per mg tissue) electron transfer capacity of complex II decreased (P=0.004) and intrinsic (relative to citrate synthase (CS) activity) LEAK increased (P<0.03) from 0 to 6h but both returned to 0h levels by 12h. Activity of CS was greater at 0 than 12 and 24h (P≤0.02). Serum creatine kinase (CK) activity was similar from -24 through 0h but increased in all horses at 6h and remained elevated through 48h (P<0.05) though not above reference ranges. Whole blood superoxide dismutase activity fluctuated throughout the 72-h collection period (P=0.03) and serum cortisol concentration displayed a circadian pattern (P<0.0001) but neither were altered by muscle collections. No other variable, including muscle mitochondrial capacities and function, blood and muscle antioxidant status and concentrations of select cytokines, and serum amyloid A, differed by time or muscle collection. Repeated gluteal collections had limited short-term or no effect on physiological markers in unstressed, mature horses except serum CK activity, which should be interpreted with caution during repeated tissue collections.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2102631-2
    ISSN 1542-7412 ; 0737-0806
    ISSN (online) 1542-7412
    ISSN 0737-0806
    DOI 10.1016/j.jevs.2024.105070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Influence of Mechanistic Target of Rapamycin (mTOR)-Regulated Anabolic Pathways on Equine Skeletal Muscle Health

    Semanchik, Pier L. / Wesolowski, Lauren T. / Ryan, Patrick J. / White-Springer, Sarah H. / Fluckey, James D.

    Journal of Equine Veterinary Science. 2023 May, v. 124 p.104281-

    2023  

    Abstract: Skeletal muscle is a highly dynamic organ that is essential for locomotion as well as endocrine regulation in all populations of horses. However, despite the importance of adequate muscle development and maintenance, the mechanisms underlying protein ... ...

    Abstract Skeletal muscle is a highly dynamic organ that is essential for locomotion as well as endocrine regulation in all populations of horses. However, despite the importance of adequate muscle development and maintenance, the mechanisms underlying protein anabolism in horses on different diets, exercise programs, and at different life stages remain obscure. Mechanistic target of rapamycin (mTOR) is a key component of the protein synthesis pathway and is regulated by biological factors such as insulin and amino acid availability. Providing a diet ample in vital amino acids, such as leucine and glutamine, is essential in activating sensory pathways that recruit mTOR to the lysosome and assist in the translation of important downstream targets. When the diet is well balanced, mitochondrial biogenesis and protein synthesis are activated in response to increased exercise bouts in the performing athlete. It is important to note that the mTOR kinase pathways are multifaceted and very complex, with several binding partners and targets that lead to specific functions in protein turnover of the cell, and ultimately, the capacity to maintain or grow muscle mass. Further, these pathways are likely altered across the lifespan, with an emphasis of growth in young horses while decreases in musculature with aged horses appears to be attributable to degradation or other regulators of protein synthesis rather than alterations in the mTOR pathway. Previous work has begun to pinpoint ways in which the mTOR pathway is influenced by diet, exercise, and age; however, future research is warranted to quantify the functional outcomes related to changes in mTOR. Promisingly, this could provide direction on appropriate management techniques to support skeletal muscle growth and maximize athletic potential in differing equine populations.
    Keywords biogenesis ; diet ; exercise ; glutamine ; horses ; insulin ; leucine ; locomotion ; longevity ; lysosomes ; mitochondria ; muscle development ; protein synthesis ; rapamycin ; skeletal muscle ; target of rapamycin proteins ; veterinary medicine ; Anabolic ; Disease ; Equine
    Language English
    Dates of publication 2023-05
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 2102631-2
    ISSN 1542-7412 ; 0737-0806
    ISSN (online) 1542-7412
    ISSN 0737-0806
    DOI 10.1016/j.jevs.2023.104281
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  4. Article ; Online: Elevated dietary selenium rescues mitochondrial capacity impairment induced by decreased vitamin E intake in young exercising horses.

    Owen, Randi N / Semanchik, Pier L / Latham, Christine M / Brennan, Kristen M / White-Springer, Sarah H

    Journal of animal science

    2022  Volume 100, Issue 8

    Abstract: Maintenance of mitochondrial health, which is supported in part by dietary antioxidants such as selenium (Se) and vitamin E (vitE), is pertinent to optimizing athletic performance. Deficiencies in Se and vitE negatively impact muscle health but ... ...

    Abstract Maintenance of mitochondrial health, which is supported in part by dietary antioxidants such as selenium (Se) and vitamin E (vitE), is pertinent to optimizing athletic performance. Deficiencies in Se and vitE negatively impact muscle health but mitochondrial adaptations to various levels of dietary Se and vitE are poorly understood. Young Quarter Horses (mean ± SD: 17.6 ± 0.9 mo) undergoing submaximal exercise training were used to test the hypothesis that a proprietary antioxidant blend containing elevated Se yeast (EconomasE, Alltech, Inc., Nicholasville, KY) would improve mitochondrial characteristics compared to Se at current requirements, even with reduced vitE intake. Horses were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to one of three custom-formulated concentrates fed at 1% BW (dry matter, DM basis) for 12 wk: 1) 100 IU vitE/kg DM and 0.1 mg Se/kg DM (CON, n = 6); 2) no added vitE plus EconomasE to provide 0.1 mg Se/kg DM (ESe1, n = 6); or 3) no added vitE plus EconomasE to provide 0.3 mg Se/kg DM (ESe3, n = 6). Samples collected at week 0 and 12 were analyzed for serum Se and middle gluteal glutathione peroxidase (GPx) and mitochondrial enzyme activities by kinetic colorimetry and mitochondrial capacities by high-resolution respirometry. Data were analyzed using mixed linear models in SAS v9.4 with repeated measures (time) and fixed effects of time, diet, and time × diet; horse(diet) served as a random effect. Serum Se tended to increase in all horses by week 12 (P = 0.08) but was unaffected by diet. Muscle GPx activity remained similar among all horses throughout the duration of the study. Mitochondrial volume density (citrate synthase [CS] activity), integrative function (cytochrome c oxidase [CCO] activity per mg protein), and integrative (per mg tissue) oxidative (P) and electron transfer (E) capacities increased from week 0 to 12 in all horses (P ≤ 0.01). Intrinsic (relative to CS) CCO activity decreased in all horses (P = 0.001), while intrinsic P and E capacities decreased only in ESe1 horses from week 0 to 12 (P ≤ 0.002). These results suggest that feeding EconomasE to provide 0.3 mg Se/kg DM may prevent adverse effects of removing 100 IU dietary vitE/kg DM on mitochondria in young horses. More research is needed to determine optimal dietary Se and vitE levels in performance horses to maximize mitochondrial energy production.
    MeSH term(s) Animals ; Antioxidants/metabolism ; Body Weight ; Dietary Supplements ; Horses ; Mitochondria/metabolism ; Selenium/metabolism ; Vitamin E/pharmacology
    Chemical Substances Antioxidants ; Vitamin E (1406-18-4) ; Selenium (H6241UJ22B)
    Language English
    Publishing date 2022-08-01
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial, Veterinary
    ZDB-ID 390959-1
    ISSN 1525-3163 ; 0021-8812
    ISSN (online) 1525-3163
    ISSN 0021-8812
    DOI 10.1093/jas/skac172
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  5. Article ; Online: The Impact of SRT2104 on Skeletal Muscle Mitochondrial Function, Redox Biology, and Loss of Muscle Mass in Hindlimb Unloaded Rats.

    Wesolowski, Lauren T / Simons, Jessica L / Semanchik, Pier L / Othman, Mariam A / Kim, Joo-Hyun / Lawler, John M / Kamal, Khaled Y / White-Springer, Sarah H

    International journal of molecular sciences

    2023  Volume 24, Issue 13

    Abstract: Mechanical unloading during microgravity causes skeletal muscle atrophy and impairs mitochondrial energetics. The elevated production of reactive oxygen species (ROS) by mitochondria and Nox2, coupled with impairment of stress protection (e.g., SIRT1, ... ...

    Abstract Mechanical unloading during microgravity causes skeletal muscle atrophy and impairs mitochondrial energetics. The elevated production of reactive oxygen species (ROS) by mitochondria and Nox2, coupled with impairment of stress protection (e.g., SIRT1, antioxidant enzymes), contribute to atrophy. We tested the hypothesis that the SIRT1 activator, SRT2104 would rescue unloading-induced mitochondrial dysfunction. Mitochondrial function in rat gastrocnemius and soleus muscles were evaluated under three conditions (10 days): ambulatory control (CON), hindlimb unloaded (HU), and hindlimb-unloaded-treated with SRT2104 (SIRT). Oxidative phosphorylation, electron transfer capacities, H
    MeSH term(s) Rats ; Animals ; Antioxidants/pharmacology ; Sirtuin 1/metabolism ; Hydrogen Peroxide/metabolism ; Oxidative Stress ; Muscle, Skeletal/metabolism ; Oxidation-Reduction ; Muscular Atrophy/metabolism ; Mitochondria/metabolism ; Hindlimb/metabolism ; Biology
    Chemical Substances Antioxidants ; Sirtuin 1 (EC 3.5.1.-) ; SRT2104 ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241311135
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