Prolonged lipid oxidation after photodynamic treatment. Study with oxidation-sensitive probe C11-BODIPY581/591.
Photodynamic treatment (PDT) is an emerging procedure for the therapy of cancer, based on photosensitizers, compounds that generate highly reactive oxygen species on illumination with visible light. Photodynamic peroxidation of cellular lipids is a consequence of PDT associated with cytolethality. We used chloromethyl dichlorodihydrofluorescein diacetate and a novel fluorescent ratiometric oxidation-sensitive probe, C11-BODIPY581/591 (C11-BO), which reports on lipid peroxidation, for visualizing oxidative stress in cells subjected to PDT with a phthalocyanine photosensitizer Pc4. With C11-BO loaded into the cells before or immediately after PDT, we observed a prolonged oxidation, which continued up to 30 min after illumination. In contrast, H2O2 caused oxidation of C11-BO only when the cells were in direct contact with H2O2. PDT-induced oxidative stress was most pronounced in vesicular perinuclear organelles, most likely photodamaged lysosomes. We hypothesize that the lysosomal localization of the prolonged oxidative stress is a consequence of the presence of redox-active iron in lysosomes. In conclusion, we have found that oxidative stress induced in cells by PDT differs from one induced by H2O2 in respect of induction of prolonged oxidation of lipids.
Sakharov
D V
DV
Department of Biochemistry of Lipids, CBLE, Utrecht University, PO Box 80 054, 3508 TB Utrecht, The Netherlands. d.sakharov@chem.uu.nl
Elstak
E D R
ED
Chernyak
B
B
Wirtz
K W A
KW
D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005227:Fatty Acids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats
D001372:Aza Compounds; C463799:BODIPY581; D005227:Fatty Acids; D017319:Photosensitizing Agents; D006861:Hydrogen Peroxide