ArticleInternational journal of molecular sciences2021
Nox2 Inhibition Regulates Stress Response and Mitigates Skeletal Muscle Fiber Atrophy during Simulated Microgravity.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- A continuum model for tissues with moderate cell density.Computers in biology and medicine · 2025Article
- Apocynin Mitigates Diabetic Muscle Atrophy by Lowering Muscle Triglycerides and Oxidative Stress.International journal of molecular sciences · 2025Article
- Mechanotransduction and Skeletal Muscle Atrophy: The Interplay Between Focal Adhesions and Oxidative Stress.International journal of molecular sciences · 2025Review
- Oxidative Stress on the Ground and in the Microgravity Environment: Pathophysiological Effects and Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Advanced glycation end products promote ROS production via PKC/p47 phox axis in skeletal muscle cells.The journal of physiological sciences : JPS · 2024Article
- Bioreactor development for skeletal muscle hypertrophy and atrophy by manipulating uniaxial cyclic strain: proof of concept.NPJ microgravity · 2024Article
- Microphysiological systems for human aging research.Aging cell · 2024Review
- The Impact of SRT2104 on Skeletal Muscle Mitochondrial Function, Redox Biology, and Loss of Muscle Mass in Hindlimb Unloaded Rats.International journal of molecular sciences · 2023Article
- Microgravity and Musculoskeletal Health: What Strategies Should Be Used for a Great Challenge?Life (Basel, Switzerland) · 2023Review
- Cellular and Molecular Signaling Meet the Space Environment.International journal of molecular sciences · 2023Article
- Chicken or Egg? Mitochondrial Phospholipids and Oxidative Stress in Disuse-Induced Skeletal Muscle Atrophy.Antioxidants & redox signaling · 2023Review
- Phytochemicals in Skeletal Muscle Health: Effects of Curcumin (fromPlants (Basel, Switzerland) · 2022Review
- Biomanufacturing in low Earth orbit for regenerative medicine.Stem cell reports · 2022Review
- Microgravity and Space Medicine.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
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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