Specificity and uniqueness of endothelial cell stress responses.

The mammalian response to cellular stresses often involves upregulation of certain stress proteins. This response is usually neither cell nor stress specific and sometimes results in cross-protection to other stresses. Endothelial cell (EC) hypoxia-associated proteins (HAP) are a unique set of stress proteins upregulated by exposure to environmental hypoxia. In the present study, the specificity of stress protein upregulation was assessed and any potential cross-protection was evaluated using DNA strand break analysis. EC cultured in 21% or 3% oxygen were exposed to single and combined cellular stresses (0% oxygen, reoxygenation, glucose deprivation, sodium arsenite, heat, or hydrogen peroxide). Although EC can upregulate various stress proteins, the HAP are specifically upregulated only with hypoxia and offer no cross-protection against other cellular stresses. Moreover, induction of other stress proteins does not alter the induction of the HAP or the effects of hypoxia in cultured EC. Thus EC display a unique specificity in regard to the stimulus for upregulation of stress proteins and are distinct from other cell types thus far examined.