The role of H2O2 as a mediator of UVB-induced apoptosis in keratinocytes.
Apoptosis is an active form of cell death that is initiated by a variety of stimuli, including reactive oxygen species (ROS) and ultraviolet (UV) radiation. Previously, it has been reported that UVB-irradiation of keratinocytes leads to intracellular generation of hydrogen peroxide (H2O2) and that antioxidants can inhibit ROS-induced apoptosis. Although both UVB-irradiation and H2O2-incubation led to increased intracellular H2O2 levels, the antioxidants catalase and glutathione monoester (GME), inhibited apoptosis only when induced by H2O2, not by UVB. Furthermore, extracellular signal-regulated kinase (ERK), a prominent member of the mitogen-activated protein kinase (MAPK) family, was found to be activated by treatment with both UVB and H2O2. Inhibition of ERK phosphorylation by pre-treatment with PD98059 resulted in enhanced apoptosis after H2O2-exposure. However,no significant difference of apoptosis was observed between cells with and without inhibitor pre-treatment upon UVB-irradiation. DNA damage in the form of cyclobutane pyrimidine dimers was observed after exposure to UVB, but no photoproducts were found in H2O2-treated cells. These results suggest a ROS-independent pathway of UVB-induced apoptosis. Although UVB-irradiation causes moderate increase in H2O2, the generation of H2O2 does not contribute to the induction of apoptosis. Moreover, activation of ERK only blocks H2O2-dependent apoptosis but has no impact on UVB-induced apoptosis.
Chang
Hong
H
Department of Dermatology, Friedrich-Schiller-University, Jena, Erfurter Strasse 35, D-07740 Jena, Germany.
Oehrl
Wolf
W
Elsner
Peter
P
Thiele
Jens J
JJ
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism; D015603:Keratinocytes / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011740:Pyrimidine Dimers; D017382:Reactive Oxygen Species; D013997:Time Factors; D014466:Ultraviolet Rays
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011740:Pyrimidine Dimers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one