ArticlePloS one2018
Role of altered proteostasis network in chronic hypobaric hypoxia induced skeletal muscle atrophy.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 47 citations in OpenAlex.
- Effects of intermittent exposure to hypobaria and cold on the microarchitecture and morphofunctional profile of rat gastrocnemius muscle.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Hypoxia-induced GRP78 activation disrupts the Fndc5/Irisin axis to accelerate skeletal muscle atrophy.Cell stress & chaperones · 2026Article
- Resveratrol reduces muscle atrophy and stress pathway activation in a combined disuse-hypoxia-mouse model.Frontiers in pharmacology · 2026Article
- Article
- miR-320-3p regulates apelin and TGF-β/SMAD3 signaling in hypobaric hypoxia exposed rats to induce skeletal muscle atrophy.Journal of physiology and biochemistry · 2025Article
- A comprehensive review on physiological and biological activities of carnosine: turning from preclinical facts to potential clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- miRNA and leptin signaling in metabolic diseases and at extreme environments.Pharmacology research & perspectives · 2024Review
- Skeletal and cardiac muscle have different protein turnover responses in a model of right heart failure.GeroScience · 2023Article
- Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation.Journal of physiology and biochemistry · 2023Article
- Exposure to High Altitude Promotes Loss of Muscle Mass That Is Not Rescued by Metformin.High altitude medicine & biology · 2022Article
- Fusion of Normoxic- and Hypoxic-Preconditioned Myoblasts Leads to Increased Hypertrophy.Cells · 2022Article
- HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia.International journal of molecular sciences · 2022Article
- Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.Frontiers in nutrition · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH).
methodsMale Sprague Dawley rats were exposed to simulated hypoxia equivalent to a pressure of 282 torr for different durations (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised from the hind limb of rats for biochemical analysis.
resultsChronic hypobaric hypoxia caused a substantial increase in protein oxidation and exhibited a greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins triggered the proteolytic systems, 20S proteasome and calpain pathway which were accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed upto 07d of CHH which was also linked with enhanced glycogen synthase kinase-3β (GSk-3β) expression, a negative regulator of Akt. Muscle-derived cytokines, tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-©) and interleukin-1β (IL-1β) levels significantly increased from 07d onwards. CHH exposure also upregulated the expression of nuclear factor kappa-B (NF-κB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1 (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub-proteasome and apoptosis pathway.
conclusionsThe disrupted proteostasis network was tightly coupled to degradative pathways, altered anabolic signaling, inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia exposure affected the protein homeostasis which overwhelms the muscular system and tends towards skeletal muscle atrophy.
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