New studies and Preliminary Data from our laboratory point suggest that the renin-angiotensin signaling (RAS) are significant sources of oxidative stress, and thus pro-fibrotic signaling in the heart. Upregulation of RAS in the aging heart upregulates the Nox2 isoform of NADPH oxidase. We have also recently found that Nox2 also contributes to oxidative stress and atrophy during ground-based spaceflight of skeletal muscle. Thus secondary and amplified oxidative stress may damage nuclei and stimulate pro-fibrotic signaling, including TGF-ß, smad2/3 phosphorylation, and collagen I accumulation. The current RFA research emphasis in Space Biology Tissue Sharing provides an opportunity to promote sharing of samples with ongoing and archived studies. We will propose a series of studies with X-Ray, HZE and X-Ray + HZE radiation. Collaboration with Dr. Nancy Turner’s laboratory at Texas A&M University will focus on two sets of radiation studies. The first cohort of studies will use X-Ray radiation (0.5 Gy) to induce damage and oxidative stress. Mouse (astronaut age) heart samples will be taken 12 hours, or 4 or 8 weeks after exposure. In the second set of experiments, mice will be exposed to 28Si and 48Ti (0.5 Gy). Mice will be terminated and tissues extracted 12 hrs, 4 wks or 8 wks after radiation exposure. Efficacy of an intervention of fish oil + pectin in reducing cardiac fibrotic signaling will be tested. Fish oil reduces oxidative stress, increases protective heat shock proteins, and cardiovascular disease. Our Preliminary Data reveal that fish oil + curcumin also reduces muscle atrophy. Dietary pectin ingestion reduces oxidative stress and apoptosis. Pectin and fish oil have also reduced radiation-induced tissue fibrosis in the kidney and liver, respectively. However, the effects on the irradiated heart are unknown. p53 contributes to apoptosis, cardiac fibrosis, and muscle atrophy. We will also query archived cardiac samples irradiated at the Brookhaven National Laboratory involved combined X-Ray and 56Fe radiation, where mice with a single p53 allele deletion and wild-types were irradiated.
This experiment is currently in progress. Results will be available at the conclusion of the study.
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