Sodium arsenic and ultraviolet-radiation synergistically induce cell injury in lens and retinal epithelial cells occurring migration of HMGB1 (IRM11P.639)

Abstract

Abstract Although sodium arsenic (As) and ultraviolet radiation (UVR) can induce cell injury through either DNA damage or reactive oxidative species (ROS) in various epithelial cells, whether damaged-associated molecular pattern (DAMP) involved in cell injury is still unclear. To determine the association of HMGB1, one of DAMP molecules that can be secreted by oxidative stress, we investigated cell injury in human lens epithelial cell (HLE B3) and human retinal epithelial cell (ARPE-19) using cell viability assay, western blot, confocal microscopy and flow cytometry (FACS analysis). In both HLE B3 and ARPE-19 cells, DNA damage marker, cleaved PARP and cell viability assay showed that UVR synergistically increased As-caused cell death(injury). During UVR and As-caused cell injury, HMGB1 was translocated from nucleus to cytosol and then secreted to extracellular region. ROS scavenger N-acetylcystein (NAC) and mito-tempo inhibited both translocation and secretion of HMGB1 in dose-dependent manner, implicating that migration of HMGB1 is closely associated with ROS generation in mitochondria. Taken together, we concluded that HMGB1 is associated in cell injury caused by UVR and As. Nevertheless how migrated HMGB1 plays a role in UVR-As caused cell injury of HLE B3 and arpe-19 cells is still unclear.