Abstract
For their remarkable biomimetic properties implying strong modulation of the intracellular and extracellular redox state, cerium oxide nanoparticles (also termed “nanoceria”) were hypothesized to exert a protective role against oxidative stress associated with the harsh environmental conditions of spaceflight, characterized by microgravity and highly energetic radiations. Nanoparticles were supplied to proliferating C2C12 mouse skeletal muscle cells under different gravity and radiation levels. Biological responses were thus investigated at a transcriptional level by RNA next-generation sequencing. Lists of differentially expressed genes (DEGs) were generated and intersected by taking into consideration relevant comparisons, which led to the observation of prevailing effects of the space environment over those induced by nanoceria. In space, upregulation of transcription was slightly preponderant over downregulation, implying involvement of intracellular compartments, with the majority of DEGs consistently over- or under-expressed whenever present. Cosmic radiations regulated a higher number of DEGs than microgravity and seemed to promote increased cellular catabolism. By taking into consideration space physical stressors alone, microgravity and cosmic radiations appeared to have opposite effects at transcriptional levels despite partial sharing of molecular pathways. Interestingly, gene ontology denoted some enrichment in terms related to vision, when only effects of radiations were assessed. The transcriptional regulation of mitochondrial uncoupling protein 2 in space-relevant samples suggests perturbation of the intracellular redox homeostasis, and leaves open opportunities for antioxidant treatment for oxidative stress reduction in harsh environments.
Highlights
IntroductionSkeletal muscle tissue alterations such as atrophy, muscle force decrease, and shift in muscle fiber composition occur during aging, pathology onset, radiation exposure, and mechanical unloading.[1−5] A fast deterioration of skeletal muscle tissue, in particular, affects astronauts who are exposed both to gravitational unloading (hereafter termed microgravity or “μg”) and to cosmic radiation during spaceflight
Skeletal muscle tissue alterations such as atrophy, muscle force decrease, and shift in muscle fiber composition occur during aging, pathology onset, radiation exposure, and mechanical unloading.[1−5] A fast deterioration of skeletal muscle tissue, in particular, affects astronauts who are exposed both to gravitational unloading and to cosmic radiation during spaceflight
This work aimed at verifying putative protection of NC against deleterious space environment effects on proliferating C2C12 mouse skeletal muscle cells, which were cultured on board the International Space Station (ISS) in two different experimental configurations, meaning either exposure to microgravity and cosmic radiations or to artificially obtained Earth gravity (1g by centrifugation) and cosmic radiations
Summary
Skeletal muscle tissue alterations such as atrophy, muscle force decrease, and shift in muscle fiber composition occur during aging, pathology onset, radiation exposure, and mechanical unloading.[1−5] A fast deterioration of skeletal muscle tissue, in particular, affects astronauts who are exposed both to gravitational unloading (hereafter termed microgravity or “μg”) and to cosmic radiation during spaceflight. In another pilot study from our group, NC was shown to decrease cell death and DNA fragmentation while promoting stemness and tissue regeneration in planarian worms exposed to low-dose radiations,[40] demonstrating potential radioprotective activity relevant to spaceflight
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