Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Abstract

Abstract. microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high-linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

Space Radiation Biology for “Living in Space”

“…These devices can equalize the gravity vector and cancel the effect of gravity, thereby simulating μG. However, there are two major limitations associated with this approach: (i) it is necessary to stop rotation during irradiation as the sample was exposed to radiation outside the incubator after or before rotation with a RWV [183][184][185][186][187][188] and (ii) nonuniformity of dose flatness in the irradiation area occurs because of chronical irradiation of a rotating sample with a RPM [189,190]. To address these problems, we have developed a system of simultaneous irradiation in simulated-μG (SSS) using 3D clinostat [191,192].…”

Stress and Radiation Responsiveness

“…Ideally, cells should be exposed to μg and different radiation qualities at the same time. However, only a limited number of studies have yet been performed in which cells are simultaneously exposed to both these physical space stressors (Beck et al 2014;Pani et al 2016;Fernandez-Gonzalo et al 2017). In a recent study simulated μg was found to increase particle radiation-induced apoptosis in B lymphoblast cells (Dang et al 2014).…”

A New System for Three-dimensional Clinostat Synchronized X-irradiation with a High-speed Shutter for Space Radiation Research

“…There is an issue with these previous studies in that it was necessary to stop the rotation during the irradiation. Another issue was that the sample on the 3D clinostat in an incubator was chronically irradiated using neutrons from californium-252 (Beck et al, 2014;Pani et al, 2016) (Fig. 1B).…”