Cyclooxygenase dependent release of heme from microsomal hemeproteins correlates with induction of heme oxygenase 1 transcription in human fibroblasts

Induction of heme oxygenase 1 transcription and enzymatic activity is a com mon response after exposure of cells to various forms of oxidative stress i ncluding ultraviolet A radiation (UVA) and hydrogen peroxide. We now show t hat UVA irradiation or hydrogen peroxide treatment of human skin fibroblast s leads to an immediate release of the heme oxygenase substrate, heme, from microsomal hemeproteins. The release of heme by UVA apparently involves cy clooxygenase activity because it is inhibited by the cyclooxygenase inhibit or indomethacin. We also demonstrate a high degree of correlation between t he amount of heme released and the degree of subsequent induction of heme o xygenase 1 transcription following UVA and hydrogen peroxide treatment. We propose that release of heme from microsomal hemeproteins determines the de gree of induction of heme oxygenase 1 transcription in human fibroblasts af ter oxidative stress. (C) 1999 Elsevier Science Inc.