Cytoprotective activity of elevated static pressure against oxidative stress in normal human fibroblasts

Abstract

DNA damage in normal cells by reactive oxygen species can trigger cellular senescence and tumorigenesis. Therefore, many strategies have been developed to inhibit DNA damage and identify molecules that can prevent various oxidative stress-related diseases, including cancer. To investigate the effect of pressure, preconditioning with two types of atmospheric pressure (hyperbaric mild hyperoxia compressed with air (EP) and hyperbaric normoxia with nitrogen gas (HN)) was applied to normal human lung fibroblasts (WI-38) for 1 or 3 days, and then cells were treated with hydrogen peroxide to induce oxidative damage. Here, we have elucidated two types of pressure that can protect WI-38 cells from oxidative stress-induced DNA damage. To profile the expression of genes that contribute to the cytoprotective effects of the pressures, microarray analyses were performed. Extracellular matrix-, cell adhesion-, and cell cycle-related genes were highly involved in the cytoprotective effects of the pressures. Among the significantly expressed genes, fibronectin was the most inducible in WI-38 cells under the cytoprotective conditions against oxidative damage. Additionally, cellular fibronectin, and not the secreted isoform, acted as a cytoprotective marker at these pressures. Together, these findings suggest that elevated static pressures exhibit cytoprotective activity against oxidative stress-induced DNA damage by inducing cellular fibronectin.