Journal
FEBS LETTERS
Volume 579, Issue 1, Pages 185-190Publisher
WILEY
DOI: 10.1016/j.febslet.2004.11.073
Keywords
photodynamic treatment; reactive oxygen species; glutathione; pentose phosphate pathway; glycolysis; apoptosis
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Photodynamic treatment (PDT) employs a photosensitizer and the light-induced formation of reactive oxygen species - antagonized by cellular antioxidant systems - for the removal of harmful cells. This study addresses the effect of altered carbohydrate metabolism on the cellular antioxidant glutathione system, and the subsequent responses to PDT. It is shown that glucose-deprivation of 18 h prior to PDT causes a reduced level of intracellular glutathione and an increased cytotoxicity of PDT. These effects can be mimicked by inhibitors of glutathione synthesis (buthionine-sulfoximine) or its regeneration (1,3-bis-(2-chlorethyl)-1-nitrosourea). Inhibited glutathione metabolism shifts the apoptotic window to lower fluences, while glucose deprivation abolishes apoptosis as a result of ATP deficiency. Our results prove evidence for manipulation of the outcome of PDT through internal metabolic pathways. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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