Abstract
UV causes damages in cellular membrane and cytoplasm via generation of reactive oxygen species (ROS) as well as damages in DNA by forming photoproducts. Investigations in this decade clearly demonstrated that two distinct UV responsive intracellular signaling pathways are present, i.e., DNA damage-dependent and -independent pathways. Our previous study has shown that activation of JNK and apoptosis in UVC-irradiated cell population were reduced in hypoxic condition whereas activation of ERK was not affected. Instead, ERK activation was reduced by an inhibitor of receptor tyrosine kinases (RTK). Therefore, contribution of the balance between JNK and ERK, which was regulated by ROS and RTK, respectively, to cell death was suggested. The role of DNA damage-independent pathway is further relevant in cellular responses to UVB. When cells were irradiated with UVB at a dose that forms equivalent amount of DNA photoproducts by UVC, generation of ROS, cell death and mitochondrial cytochrome C release were higher in UVB-irradiated cells. Furthermore, phosphorylation of p53 at ser392 was markedly observed in UVB-irradiated cells that were inhibited by a p38 inhibitor and by an antioxidant. These results indicated the significance of ROS-p38 pathway in UVB irradiated cells, which may act as a protective mechanism against tumorigenesis by eliminating damaged cells. The combinations of acute stress responses as shown above and chronic responses, probably via production of soluble secondary factors, should be examined to better understand UV stress responses in our daily life.
