Modulation of gene expression by the oxidative stress generated in human skin cells by UVA radiation and the restoration of redox homeostasis.
UVA radiation generates a significant oxidative stress in skin cells which is further enhanced by the release of the pro-oxidant catalysts iron and heme, and exacerbated by UVA-mediated destruction of cellular reducing equivalents and the antioxidant enzyme catalase. An important consequence of this altered redox state is the generation of oxidized membrane components in the form of 4-hydroxynonenal, ceramides and oxidized phospholipids, all of which are potent signalling molecules which lead to modulation of the expression of many genes. Transcription factors (such as nuclear factor kappa-light-chain-enhancer of activated B cells) and several genes (e.g. interleukins, intercellular adhesion molecule and 1, hemeoxygenase 1) involved in the inflammatory response are dramatically modified by UVA. Levels of both antioxidant and pro-oxidant proteins, including manganese-dependent superoxide dismutase, glutathione peroxidase, hemeoxygenase 1, NADPH oxidase, ferritin, and methionine-S-sulfoxidereductase, are increased by UVA treatment and following moderate dose levels these will contribute to either the restoration or a further perturbation of redox homeostasis. Finally, UVA induces a whole set of matrix metalloproteinases and proteases, primarily in cells of dermal origin, which can contribute to the long-term consequences of UVA exposure of skin.
Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK. prsrmt@bath.ac.uk
Rex M
RM
Tyrrell
D005786:Gene Expression Regulation / Q000528:radiation effects*; D006706:Homeostasis; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*
D017382:Reactive Oxygen Species