Role of nitric oxide, cAMP and cGMP in the radiation induced changes of tight junctions in Madin-Darby canine kidney cells.

Radiation induced inflammatory response is thought to be the consequence of acute and chronic oxidative stress, as well as the increased production of various intercellular mediators. Nitric oxide (NO) originated reactive nitrogen species, cGMP and cAMP are well known regulatory factors of the structure and functions of cell contacts. These data raise the possibility that they may play a role in the radiation induced alterations of tight junctions (TJs) and consequently in the radiation injury of surface tissues. Using immunohistochemical methods on confluent cultures of Madin-Darby canine kidney (MDCK) cells, our goal was to clarify the possible role of NO and its relationship with the cGMP and cAMP second messenger systems in the development of the radiation induced alterations of TJs. We found that increased levels of cAMP and/or inhibition of nitrogen oxide synthase (NOS) activity both tend to strengthen TJ associated cell-to-cell contacts in unirradiated control cells. In contrast increased level of cGMP and/or increased expression of NO-sythase, caused the and irregular staining of TJal complexes, which is commonly observed in irridated cells. Our experiments also indicated the protective role of the experimentally increased cAMP level and of NOS inhibitors against the radiation induced TJ changes. All these results suggest the key role of NO in the early radiation response of TJs.