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dc.contributor.authorSalem, Mohamed M.A.*
dc.contributor.authorShalbaf, Mohammad*
dc.contributor.authorGibbons, Nick C.*
dc.contributor.authorChavan, Bhavan*
dc.contributor.authorThornton, M. Julie*
dc.contributor.authorSchallreuter, Karin U.*
dc.date.accessioned2014-04-28T11:18:23Z
dc.date.available2014-04-28T11:18:23Z
dc.date.issued2009
dc.identifier.citationSalem, M. M., Shalbaf, M., Gibbons, N. C., Chavan, B., Thornton, J. M., Schallreuter, K. U. (2009) Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage. FASEB Journal, 23(11), 3790-3807.
dc.identifier.urihttp://hdl.handle.net/10454/6168
dc.description.abstractVitiligo is characterized by a patchy loss of inherited skin color affecting approximately 0.5% of individuals of all races. Despite the absence of the protecting pigment and the overwhelming evidence for hydrogen peroxide (H(2)O(2))-induced oxidative stress in the entire epidermis of these patients, there is neither increased photodamage/skin aging nor a higher incidence for sun-induced nonmelanoma skin cancer. Here we demonstrate for the first time increased DNA damage via 8-oxoguanine in the skin and plasma in association with epidermal up-regulated phosphorylated/acetylated p53 and high levels of the p53 antagonist p76(MDM2). Short-patch base-excision repair via hOgg1, APE1, and polymerasebeta DNA repair is up-regulated. Overexpression of Bcl-2 and low caspase 3 and cytochrome c levels argue against increased apoptosis in this disease. Moreover, we show the presence of high epidermal peroxynitrite (ONOO(-)) levels via nitrotyrosine together with high nitrated p53 levels. We demonstrate by EMSA that nitration of p53 by ONOO(-) (300 x 10(-6) M) abrogates DNA binding, while H(2)O(2)-oxidized p53 (10(-3) M) enhances DNA binding capacity and prevents ONOO(-)-induced abrogation of DNA binding. Taken together, we add a novel reactive oxygen species to the list of oxidative stress inducers in vitiligo. Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1096/fj.09-132621
dc.subjectAdult
dc.subjectApoptosis; Physiology
dc.subjectAtaxia Telangiectasia Mutated Proteins
dc.subjectCaspase 3; Biosynthesis
dc.subjectCell cycle proteins; Metabolism
dc.subjectCytochromes c
dc.subjectDNA
dc.subjectDNA damage; Drug effects
dc.subjectDNA repair
dc.subjectDNA-binding proteins
dc.subjectElectrophoretic mobility shift assay
dc.subjectEpidermis
dc.subjectGuanosine; Analogs & derivatives
dc.subjectHumans
dc.subjectHydrogen peroxide; Pharmacology
dc.subjectMiddle aged
dc.subjectOxidation-reduction
dc.subjectOxidative stress
dc.subjectPeroxynitrous acid
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProto-Oncogene Proteins c-bcl-2
dc.subjectProto-Oncogene Proteins c-mdm2
dc.subjectTumor Suppressor Protein p53
dc.subjectTumor Suppressor Proteins
dc.subjectUp-Regulation
dc.subjectVitiligo
dc.subjectp300-CBP Transcription Factors
dc.subjectREF 2014
dc.titleEnhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage
dc.typeArticle


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