Abstract |
The oxidative stress triggered by photodynamic therapy ( PDT) involves generation of cytotoxic reactive oxygen species, including superoxide radical, accumulation of de novo-generated ceramide, and induction of apoptosis. Since PDT with the photosensitizer phthalocyanine Pc 4 induces mitochondrial damage and the superoxide scavenger manganese superoxide dismutase (MnSOD) is localized to mitochondria, here we tested genetically the role of MnSOD in apoptosis and ceramide accumulation after photosensitization with Pc 4. Jurkat cells overexpressing wild-type MnSOD were protected from Pc 4-PDT-initiated apoptosis, but not from increased ceramide response to Pc 4-PDT. In Jurkat cells overexpressing mutant MnSOD, however, DEVDase activation and ceramide formation were promoted post-Pc 4-PDT. Similarly, in MnSOD-null cells, Pc 4-PDT-induced apoptosis, as well as ceramide accumulation, were enhanced compared to their normal counterparts. The data show that MnSOD affects sensitivity of cells to Pc 4-PDT-initiated apoptosis, and partly ceramide accumulation, suggesting that the processes are superoxide-mediated.
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Authors | Vladislav Dolgachev, Larry W Oberley, Ting-Ting Huang, Janice M Kraniak, Michael A Tainsky, Kentaro Hanada, Duska Separovic |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 332
Issue 2
Pg. 411-7
(Jul 01 2005)
ISSN: 0006-291X [Print] United States |
PMID | 15894290
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Indoles
- Photosensitizing Agents
- phthalocyanine Pc 4
- Superoxide Dismutase
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Topics |
- Animals
- Apoptosis
(drug effects, radiation effects)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Fibroblasts
(drug effects, enzymology, radiation effects)
- Humans
- Indoles
(administration & dosage)
- Jurkat Cells
- Light
- Mice
- Photochemotherapy
(methods)
- Photosensitizing Agents
(administration & dosage)
- Superoxide Dismutase
(metabolism)
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