Even after UVA-exposure will nitric oxide protect cells from reactive oxygen intermediate-mediated apoptosis and necrosis

Reactive oxygen species (ROS) play a pivotal role in UVA induced cell damag e, As expression of the inducible nitric oxide synthase (iNOS) is a normal response of human skin to UV radiation we examined the role of nitric oxide (NO) as a protective agent during or even after UVA(1)- or ROS-exposure ag ainst apoptosis or necrosis of rat endothelial cells. When added during or UP to 2 h subsequent to UVA(1) or ROS exposure the NO-donor S-nitroso cyste ine (SNOC) at concentrations from 100-1000 muM significantly protects from both apoptosis as well as necrosis, The NO-mediated protection strongly cor relates with complete inhibition of lipid peroxidation (sixfold increase of malonedialdehyde formation in untreated versus 1.2 fold with 1 mM SNOC). N O-mediated protection of membrane function was also shown by the inhibition of cytochrome c leakage in UVA(1) treated cells, a process not accompanied by alterations in Bax and Bcl-2 protein levels. Thus, the experiments pres ented demonstrate that NO exposure during or even after a ROS-mediated toxi c insult fully protects from apoptosis or necrosis by maintaining membrane integrity and function.