繰返引張ひずみによる核の形態変化と細胞紫外線耐性向上の可能性

抄録

Ultraviolet (UV) radiation exerts adverse effects on genome stability, alters the normal state of life, and causes many diseases by inducing DNA damage. Although mechanical stimulation, such as stretching and compressing, to cells has beneficial effects in the prevention and treatment of diseases, whether it influences the nuclear morphology and/or intranuclear functions associated with DNA damage remains unknown. In this study, we investigated the effects of mechanical stimulation by cyclic stretching on nuclear morphology and resistance to UV radiation of DNA in epithelial-like cells derived from Xenopus laevis (XTC-YF). Cells adhering to silicone membranes were subjected to 10% cyclic uniaxial stretch at a frequency of 0.5 Hz for 12 h. We observed that the intracellular actin cytoskeleton and nucleus became elongated and aligned with the direction ofzero normal strain (∼62° with respect to the stretch direction) following the cyclic stretch exposure. The fluorescent intensity ofintranuclear DNA, which represents the DNA density, increased significantly. The intercellular tension, assessed by the retraction of cells upon detachment from the silicone membrane, also increased following the cyclic stretch exposure. Furthermore, UV radiation-induced DNA damage, estimated by the fluorescent intensity ofphospho-histone γ-H2AX, was significantly inhibited following the cyclic stretch exposure. These results indicate that cyclic stretch-induced morphological changes ofthe nucleus possibly improve the UV radiation resistance in XTC-YF cells, and this improvement may be caused by intracellular force-induced chromatin condensation. To our knowledge, this study is the first to demonstrate the inhibition of UV radiation-induced DNA damage by mechanical stimulation.