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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.
Afiliação
  • Wesolowski LT; Department of Animal Science, College of Agriculture and Life Science, Texas A&M University and Texas A&M AgriLife Research, College Station, TX 77843, USA.
  • Simons JL; Department of Animal Science, College of Agriculture and Life Science, Texas A&M University and Texas A&M AgriLife Research, College Station, TX 77843, USA.
  • Semanchik PL; Department of Animal Science, College of Agriculture and Life Science, Texas A&M University and Texas A&M AgriLife Research, College Station, TX 77843, USA.
  • Othman MA; Department of Kinesiology & Sport Management, School of Education and Human Development, Texas A&M University, College Station, TX 77843, USA.
  • Kim JH; Department of Kinesiology & Sport Management, School of Education and Human Development, Texas A&M University, College Station, TX 77843, USA.
  • Lawler JM; Department of Kinesiology & Sport Management, School of Education and Human Development, Texas A&M University, College Station, TX 77843, USA.
  • Kamal KY; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • White-Springer SH; Department of Kinesiology & Sport Management, School of Education and Human Development, Texas A&M University, College Station, TX 77843, USA.
Int J Mol Sci ; 24(13)2023 Jul 06.
Article em En | MEDLINE | ID: mdl-37446313
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, H2O2 production, and oxidative and antioxidant enzymes were quantified using high-resolution respirometry and colorimetry. In the gastrocnemius, (1) integrative (per mg tissue) proton LEAK was lesser in SIRT than in HU or CON; (2) intrinsic (relative to citrate synthase) maximal noncoupled electron transfer capacity (ECI+II) was lesser, while complex I-supported oxidative phosphorylation to ECI+II was greater in HU than CON; (3) the contribution of LEAK to ECI+II was greatest, but cytochrome c oxidase activity was lowest in HU. In both muscles, H2O2 production and concentration was greatest in SIRT, as was gastrocnemius superoxide dismutase activity. In the soleus, H2O2 concentration was greater in HU compared to CON. These results indicate that SRT2104 preserves mitochondrial function in unloaded skeletal muscle, suggesting its potential to support healthy muscle cells in microgravity by promoting necessary energy production in mitochondria.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sirtuína 1 / Antioxidantes Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sirtuína 1 / Antioxidantes Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos