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Nox2 Inhibition Regulates Stress Response and Mitigates Skeletal Muscle Fiber Atrophy during Simulated Microgravity.
Lawler, John M; Hord, Jeffrey M; Ryan, Pat; Holly, Dylan; Janini Gomes, Mariana; Rodriguez, Dinah; Guzzoni, Vinicius; Garcia-Villatoro, Erika; Green, Chase; Lee, Yang; Little, Sarah; Garcia, Marcela; Hill, Lorrie; Brooks, Mary-Catherine; Lawler, Matthew S; Keys, Nicolette; Mohajeri, Amin; Kamal, Khaled Y.
Afiliação
  • Lawler JM; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Hord JM; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Ryan P; Department of Molecular Physiology & Biophysics, University of Iowa, Iowa City, IA 52242, USA.
  • Holly D; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Janini Gomes M; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Rodriguez D; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Guzzoni V; Brigham & Women's Hospital, Harvard Medical School, Cambridge, MA 02115, USA.
  • Garcia-Villatoro E; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Green C; Department of Kinesiology, University of Texas Rio Grande Valley, Harlingen, TX 78539, USA.
  • Lee Y; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Little S; Department of Cellular and Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba 58059900, Brazil.
  • Garcia M; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Hill L; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Brooks MC; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Lawler MS; Brigham & Women's Hospital, Harvard Medical School, Cambridge, MA 02115, USA.
  • Keys N; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
  • Mohajeri A; School of Medicine, University of North Carolina, Chapel Hill, NC 27516, USA.
  • Kamal KY; Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Graduate Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Int J Mol Sci ; 22(6)2021 Mar 23.
Article em En | MEDLINE | ID: mdl-33806917
Insufficient stress response and elevated oxidative stress can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight and bedrest). Perturbations in heat shock proteins (e.g., HSP70), antioxidant enzymes, and sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked to unloading-induced atrophy. We recently discovered that the sarcolemmal NADPH oxidase-2 complex (Nox2) is elevated during unloading, downstream of angiotensin II receptor 1, and concomitant with atrophy. Here, we hypothesized that peptidyl inhibition of Nox2 would attenuate disruption of HSP70, MnSOD, and sarcolemmal nNOS during unloading, and thus muscle fiber atrophy. F344 rats were divided into control (CON), hindlimb unloaded (HU), and hindlimb unloaded +7.5 mg/kg/day gp91ds-tat (HUG) groups. Unloading-induced elevation of the Nox2 subunit p67phox-positive staining was mitigated by gp91ds-tat. HSP70 protein abundance was significantly lower in HU muscles, but not HUG. MnSOD decreased with unloading; however, MnSOD was not rescued by gp91ds-tat. In contrast, Nox2 inhibition protected against unloading suppression of the antioxidant transcription factor Nrf2. nNOS bioactivity was reduced by HU, an effect abrogated by Nox2 inhibition. Unloading-induced soleus fiber atrophy was significantly attenuated by gp91ds-tat. These data establish a causal role for Nox2 in unloading-induced muscle atrophy, linked to preservation of HSP70, Nrf2, and sarcolemmal nNOS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / Ausência de Peso / Atrofia Muscular / Fibras Musculares Esqueléticas / NADPH Oxidase 2 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / Ausência de Peso / Atrofia Muscular / Fibras Musculares Esqueléticas / NADPH Oxidase 2 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos