Source:http://linkedlifedata.com/resource/pubmed/id/20619338
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2010-8-13
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pubmed:abstractText |
Psoralens are regularly used in therapy in combination with ultraviolet A light irradiation (PUVA) to treat skin diseases such as psoriasis, vitiligo, and mycosis fungoides. PUVA therapy is also used within the scope of extracorporeal photopheresis to treat a variety of diseases that have a suspected involvement of pathogenic T cells, including rejection of organ transplants, graft-vs-host disease, cutaneous T cell lymphoma, and autoimmune disorders. Because psoralens are the only photosensitizers used in PUVA therapies and are considered to be responsible for a number of side effects, the identification of alternative drugs is of practical interest. Here we investigated the impact of activated Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a hydrophilic vitamin E analog lacking the phytyl tail, as an alternative photoactivatable agent with T cell cytotoxic properties. Despite the well-known antioxidative capacity of Trolox, we found that at low UVA doses and in the presence of supraphysiological concentration of nitrite, a natural constituent of human skin, this compound selectively enhances radical-mediated cytotoxicity toward T cells but not toward human skin fibroblasts, keratinocytes, or endothelial cells. The cytotoxic mechanism comprises a reaction of Trolox with photo-decomposition products of nitrite, which leads to increased Trolox phenoxyl radical formation, increased intracellular oxidative stress, and a consecutive induction of apoptosis and necrosis in fast proliferating T cells. Thus, the identified UVA/nitrite-induced phenoxyl radical formation provides an opportunity for a new cytotoxic photodynamic therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6-hydroxy-2,5,7,8-tetramethylchroman...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromans,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Phenols,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Sensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/phenoxy radical
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1873-4596
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1129-37
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pubmed:meshHeading |
pubmed-meshheading:20619338-Apoptosis,
pubmed-meshheading:20619338-Chromans,
pubmed-meshheading:20619338-Humans,
pubmed-meshheading:20619338-Jurkat Cells,
pubmed-meshheading:20619338-Nitrites,
pubmed-meshheading:20619338-Oxidative Stress,
pubmed-meshheading:20619338-PUVA Therapy,
pubmed-meshheading:20619338-Phenols,
pubmed-meshheading:20619338-Radiation-Sensitizing Agents,
pubmed-meshheading:20619338-Skin,
pubmed-meshheading:20619338-T-Lymphocytes,
pubmed-meshheading:20619338-Ultraviolet Rays
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pubmed:year |
2010
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pubmed:articleTitle |
UVA-induced phenoxyl radical formation: A new cytotoxic principle in photodynamic therapy.
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pubmed:affiliation |
Department of Plastic and Reconstructive Surgery, Hand Surgery, and Burn Center, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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