SPECIFICITY AND UNIQUENESS OF ENDOTHELIAL-CELL STRESS RESPONSES

The mammalian response to cellular stresses often involves upregulatio n of certain stress proteins. This response is usually neither cell no r stress specific and sometimes results in cross-protection to other s tresses. Endothelial cell (EC) hypoxia-associated proteins (HAP) are a unique set of stress proteins upregulated by exposure to environmenta l hypoxia. In the present study, the specificity of stress protein upr egulation was assessed and any potential cross-protection was evaluate d using DNA strand break analysis. EC cultured in 21% or 3% oxygen wer e exposed to single and combined cellular stresses (0% oxygen, reoxyge nation, glucose deprivation, sodium arsenite, heat, or hydrogen peroxi de). Although EC can upregulate various stress proteins, the HAP are s pecifically upregulated only with hypoxia and offer no cross-protectio n against other cellular stresses. Moreover, induction of other stress proteins does not alter the induction of the HAP or the effects of hy poxia in cultured EC. Thus EC display a unique specificity in regard t o the stimulus for upregulation of stress proteins and are distinct fr om other cell types thus far examined.