In vivo space radiation-induced non-targeted responses: late effects on molecular signaling in mitochondria

Abstract

The lack of clear knowledge about space radiation-induced biological effects has been singled out as the most important factor limiting the prediction of radiation risk associated with human space exploration. The expression of space radiation-induced non-targeted effects is thought to impact our understanding of the health risks associated with exposure to low fluences of particulate radiation encountered by astronauts during prolonged space travel. Following a brief review of radiation-induced bystander effects and the growing literature for the involvement of oxidative metabolism in their expression, we show novel data on the induction of in vivo non-targeted effects following exposure to 1100 MeV/nucleon titanium ions. Analyses of proteins by two-dimensional gel electrophoresis in non-targeted liver of cranially-irradiated Sprague Dawley rats revealed that the levels of key proteins involved in mitochondrial fatty acid metabolism are decreased. In contrast, those of proteins involved in various cellular defense mechanisms, including antioxidation, were increased. These data contribute to our understanding of the mechanisms underlying the biological responses to space radiation, and support the involvement of mitochondrial processes in the expression of radiation induced non-targeted effects. Significantly, they reveal the cross-talk between propagated stressful effects and induced adaptive responses. Together, with the accumulating data in the field, our results may help reduce the uncertainty in the assessment of the health risks to astronauts. They further demonstrate that 'network analyses' is an effective tool towards characterizing the signaling pathways that mediate the long-term biological effects of space radiation.

Fig. (1)

A simplified schematic of the structure of the mitochondrion

Fig. (2)

Proteins down-regulated in mitochondria of non-targeted liver of rats whose head was exposed 20 months earlier to 1100 MeV/nucleon titanium ions participate in fatty acid elongation in mitochondria. (The down-regulated proteins (highlighted in green) are 3-ketoacyl CoA thiolase and mitochondrial trifunctional protein alpha subunit).

Fig. (3)

Up-regulated carboxylesterase and DNAJC3 (heat shock proteins) in mitochondria of non-targeted liver of rats whose head was exposed 20 months earlier to 1100 MeV/nucleon titanium ions participate in cell survival functions (NCOA: Nuclear receptor coactivator 1; RXRα: Retinoid receptor α; PXR: Pregnane X receptor; Nrf2: NF-E2-related factor 2; ARE/EpRE: Antioxidant response element/Electrophile response element; DNAJC3: DnaJ homolog subfamily C member 3)