NOX2 deficiency exacerbates diet-induced obesity and impairs molecular training adaptations in skeletal muscle

Henriquez-Olguin, Carlos; Meneses-Valdes, Roberto; Raun, Steffen H.; Gallero, Samantha; Knudsen, Jonas R.; Li, Zhencheng; Li, Jingwen; Sylow, Lykke; Jaimovich, Enrique; Jensen, Thomas E.

doi:10.1016/j.redox.2023.102842

Cited by 9 publications

(2 citation statements)

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“…5 ). Physical activity on Earth causes muscle growth and mitochondrial biogenesis, and triggers a physiological balance of ROS generation and antioxidant responses that are fundamental features of muscle health ad performance 67 . Inactivity on Earth triggers rapid muscle atrophy 68 but minor mitochondrial changes in the same timeframe 39 , suggesting that ROS production is low and/or efficiently counteracted by cellular defenses.…”

Section: Discussionmentioning

confidence: 99%

Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts

Murgia,

Rittweger,

Reggiani

et al. 2024

npj Microgravity

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Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.

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Section: Discussionmentioning

confidence: 99%

Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts

Murgia,

Rittweger,

Reggiani

et al. 2024

npj Microgravity

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“…However, NOXs inhibitors have yet to be considered clinically as their oxidative roles have physiological significance [39]. NOX2deficient mice on high-fat diets developed severe glucose metabolism disorders, suggesting that the NOX enzymes may be a sensitive target to modulate Dox cardiotoxicity [40].…”

Section: Nadph Oxidases Nitric Oxide Synthases and Xanthine Oxidasementioning

confidence: 99%

Different Mechanisms in Doxorubicin-Induced Cardiomyopathy: Impact of BRCA1 and BRCA2 Mutations

Nguyen,

Frisbee,

Singh

2024

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Germline mutations in Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) cause breast, ovarian, and other cancers, and the chemotherapeutic drug doxorubicin (Dox) is widely used to treat these cancers. However, Dox use is limited by the latent induction of severe cardiotoxicity known as Dox-induced cardiomyopathy, for which there are no specific treatments currently available. Dox is administered into the systemic circulation, where it readily translocates into sub-cellular compartments and disrupts the integrity of DNA. Accumulating evidence indicates that oxidative stress, DNA damage, inflammation, and apoptosis all play a central role in Dox-induced cardiomyopathy. The BRCA1 and BRCA2 proteins are distinct as they perform crucial yet separate roles in the homologous recombination repair of DNA double-strand breaks, thereby maintaining genomic integrity. Additionally, both BRCA1 and BRCA2 mitigate oxidative stress and apoptosis in both cardiomyocytes and endothelial cells. Accordingly, BRCA1 and BRCA2 are essential regulators of pathways that are central to the development of cardiomyopathy induced by Doxorubicin. Despite extensive investigations, there exists a gap in knowledge about the role of BRCA1 and BRCA2 in Doxorubicin-induced cardiomyopathy. Here, we review the previous findings and associations about the expected role and associated mechanisms of BRCA1 and 2 in Dox-induced cardiomyopathy and future perspectives.

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