Ultraviolet B-induced cell death in four cutaneous cell lines exhibiting different enzymatic antioxidant defences: involvement of apoptosis.
Reactive oxygen species (ROS) play a role in the modulation of apoptosis. Antioxidant defence mechanisms against cell death involving apoptosis due to UVB irradiation were studied on three established cell lines (SCC derived from human skin squamous cell carcinoma, F-SV and F-ST derived from human skin fibroblasts) which were susceptible to cell death by UVB irradiation (12.5-250 mJ/cm2), and one cell line (N-F) derived from primary cultured human skin fibroblasts which was resistant to cell death. We compared antioxidant defences between the three established cell lines and N-F, measuring four antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) and a non-enzymatic antioxidant glutathione. The greatest difference was that Cu, Zn-SOD activity in N-F was 3-4-times the three other cell lines. Though SCC had much larger amounts of glutathione and higher antioxidant enzyme activities except for Cu, Zn-SOD than N-F, SCC was very susceptible to cell death. After UVB irradiation (at 16 h after 12.5 mJ/cm2), in all cell lines, SOD activity increased 1.1-1.3-times that of non-irradiated cells, while other enzyme activities remained constant. This presumably represents a protective response against ROS generated during UVB irradiation. N-F which was resistant to UVB-induced cell death had higher Cu, Zn-SOD activity before UVB irradiation, and a larger increase of SOD (mainly Mn-SOD) after UVB exposure than the other cell lines which were susceptible to cell death. Therefore, we conclude that the most important enzymatic antioxidant to protect cells from UVB damage is SOD.
Department of Biochemistry, Shinshu University, School of Medicine, Matsumoto, Japan.
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Shindo
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Hashimoto
D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000502:physiology; D012867:Skin / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000963:Antimetabolites; D000975:Antioxidants; D008054:Lipid Peroxides; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione