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.

Prenatal hyperbaric normoxia treatment improves healthspan and regulates chitin metabolic genes in Drosophila melanogaster

“…2E). These results suggest that HN plays a protective role against different stresses in Drosophil a, which is in agreement with previous in vitro reports [16]. …”

“…We found no change in starvation resistance, but this could be correlated with a number of other life-history traits, including body size. Thus, our study provides additional independent evidence for the use of HN-induced mild stress as a hormetic effector in Drosophila , as was suggested by a previous in vitro study [16]. …”

“…We previously showed that hyperbaric normoxia protects normal fibroblasts (WI-38) against oxidative stress [16]. We therefore examined whether HN treatment also enhanced stress tolerance in D. melanogaster (Table 1A).…”

“…We previously reported that hyperbaric normoxia (HN, 2 atmospheres absolute with 10% O 2 ) as a mechanical mild stressor shows hormetic effects, such as inducing a cytoprotective response in vitro by regulating fibro-nectin expression and DNA damage [16]. Mechanical stress caused by stretching, compression, fluid shear stress, or hydrostatic pressure is the primary regulator to induce homeostatic mechanisms.…”

“…Hyperbaric normoxia stress shows no genotoxicity on various cell lines, and in fact shows cytoprotective effects [16]. However, evidence that these hormetic effects of HN also occur in vivo is lacking.…”