微小重力環境下で誘発される細胞骨格および細胞核の構造変化とDNA損傷

抄録

Microgravity due to long-term spaceflight induces physiological disorders such as bone loss and muscle atrophy. Although studies on changes in biochemical signaling pathways and gene expression in cells exposed to microgravity have mainly been conducted, the effects of microgravity on the intracellular mechanical structures such as the cytoskeletons and nucleus remain poorly understood. Here, we investigated in detail the changes in the morphology of the actin cytoskeleton and the nucleus of human skin fibroblasts 24 hours after exposure to microgravity using a clinostat device that produces an environment similar to that of outer space (10^–3 G) by rotating the sample around two axes, and analyzed changes in DNA damage within the nucleus. Furthermore, we precisely measured the surface morphology and surface mechanical properties of cells using atomic force microscopy (AFM) to examine the relationship between changes in intracellular forces induced by microgravity and DNA damages. Exposure of cells to microgravity significantly increased DNA damage within the nucleus. Microgravity also reduced the internal mechanical tension in the actin cytoskeleton and decreased the expression level of the nuclear lamina, suggesting a reduction in nuclear mechanical strength. Simultaneously, a decrease in compressive forces acting on the nucleus induced deformation of the nuclear lamina resulting in the nuclear shrinkage. These findings suggest that such changes in the intracellular mechanical structures under microgravity might be closely involved in inducing intranuclear DNA damage.