Role of phagocyte oxidase in UVA-induced oxidative stress and apoptosis in keratinocytes.
Chronic exposure to ultraviolet radiation including ultraviolet A (315-400 nm) (UVA) may cause photocarcinogenesis and photoaging. The UVA-induced production of reactive oxygen species (ROS) and the resultant oxidative stress exposure play an important role in these biological processes. Here we have investigated the role of phagocyte oxidase (PHOX, gp91phox) in the production of ROS, redox status change, and apoptosis after UVA exposure by using gp91phox-deficient (gp91phox-/-) primary keratinocytes. UVA radiation resulted in increased ROS production and oxidation of reduced glutathione (GSH) to its oxidized form (GSSG). The presence of diphenylene iodonium (DPI) inhibited ROS production by UVA. In comparison with wild-type cells, gp91phox-/- cells produced slightly less ROS and GSH oxidation. UVA radiation induced apoptosis in wild-type keratinocytes as detected by phosphatidylserine (PS) translocation, caspase activation, and DNA fragmentation. As compared with wild-type cells, UVA induced less PS translocation in gp91phox-deficient cells. No difference, however, was observed in caspase activation and DNA fragmentation after UVA exposure in wild-type and gp91phox-/- cells. These findings suggest that gp91phox plays a limited role in the UVA-induced ROS production, oxidative stress, and therefore the PS translocation, but has no effect on UVA-induced caspase activation and DNA fragmentation during apoptosis.
He
Yu-Ying
YY
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. he3@niehs.nih.gov
Huang
Jian-Li
JL
Block
Michelle L
ML
Hong
Jau-Shyong
JS
Chignell
Colin F
CF
D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D020169:Caspases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
D008562:Membrane Glycoproteins; D009861:Onium Compounds; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020169:Caspases; D005978:Glutathione