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Title: Nitric oxide as a regulator of apoptosis and inflammation in human skin following ultraviolet irradiation
Author: Mowbray, Megan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Since the finding that NO released from smooth muscle vascular endothelium has vasodilatory properties, there has been a surge in research designed to further elucidate the biological roles of this free radical. Enzyme-dependent and enzyme-independent mechanisms of NO generation have been observed in human skin. NO generation by both mechanisms increases following ultraviolet radiation (UVR). In vivo murine data suggests that NO has an anti-apoptotic role in human skin following UVR. In the work presented in this thesis I have shown that zeolite NO (Ze-NO) is an inert topical NO donor which releases physiologically relevant concentrations of NO. The NO released by Ze-NO induces minimal cutaneous inflammation, in contrast to earlier NO donors investigated. I provide evidence to show that NO is stored in the form of nitrosospecies in human skin and sweat on the skin surface. NO release from nitrosospecies stores occurs within 30 minutes of exposure to UVR. I provide preliminary in vivo human data which suggests that NO is acting anti-apoptotically in human skin following UVR. NO had no significant effect on DNA damage or repair following UVR. Finally, I provide evidence that a control mechanism for the upregulation of iNOS exists in human skin in the form of arginase and the urea cycle. In order to develop our understanding of the role of NO in human skin, all the work presented in this thesis has been carried out in vivo in human subjects. NO has complex pleiotropic actions which depend upon the concentration of NO, the target cell and the microenvironment. In vivo clinical research, using physiologically relevant parameters, is therefore essential if we are to further our knowledge of this free radical.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available