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 common response after exposure of cells to various forms of oxidative stress including ultraviolet A radiation (UVA) and hydrogen peroxide. We now show that UVA irradiation or hydrogen peroxide treatment of human skin fibroblasts leads to an immediate release of the heme oxygenase substrate, heme, from microsomal hemeproteins. The release of heme by UVA apparently involves cyclooxygenase activity because it is inhibited by the cyclooxygenase inhibitor indomethacin. We also demonstrate a high degree of correlation between the amount of heme released and the degree of subsequent induction of heme oxygenase 1 transcription following UVA and hydrogen peroxide treatment. We propose that release of heme from microsomal hemeproteins determines the degree of induction of heme oxygenase 1 transcription in human fibroblasts after oxidative stress.
Kvam
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The Department of Pharmacy and Pharmacology, University of Bath, UK.
Noel
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Basu-Modak
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Tyrrell
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RM
D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics*; D051547:Heme Oxygenase-1; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D016861:Cyclooxygenase Inhibitors; D006420:Hemeproteins; D008565:Membrane Proteins; D002084:Butylated Hydroxytoluene; D006418:Heme; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin