| Abstract | Among the cellular responses to photodamage initiated by photodynamic therapy (PDT) are autophagy and apoptosis. While autophagy is a reversible process that can be both a survival and a death pathway, apoptosis is irreversible, leading only to cell death. In this study, we followed the fate of mouse leukemia L1210 cells after photodamage to the endoplasmic reticulum (ER) using a porphycene photosensitizer, where Bcl-2 was among the PDT targets. In wild-type cells, we observed a rapid wave of autophagy, presumed to represent the recycling of some damaged organelles, followed by apoptosis. Using shRNA technology, we created a Bax knockdown line (L1210/Bax(-)). In the latter cell line, we found a marked decrease in apoptosis after photodamage or pharmacologic inactivation of Bcl-2 function, but this did not affect PDT efficacy. Loss of viability was associated with a highly-vacuolated morphology consistent with autophagic cell death. Previous studies indicated pro-survival attributes of autophagy after low-dose PDT, suggesting that autophagy may be responsible for the 'shoulder' on the dose-response curve. It appears that attempts at extensive recycling of damaged organelles are associated with cell death, and that this phenomenon is amplified when apoptosis is suppressed. |
| Authors | David Kessel, Adelaida Segarra Arroyo
(Affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.)
|
| Journal | Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
(Photochem Photobiol Sci)
Vol. 6
Issue 12
Pg. 1290-5
(Dec 2007)
ISSN: 1474-905X England |
| PMID | 18046484
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
| Chemical References |
- Atg7 protein, mouse
- Microtubule-Associated Proteins
- Photosensitizing Agents
- Porphyrins
- Proto-Oncogene Proteins c-bcl-2
- porphycene
|
| Topics |
- Animals
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Blotting, Western
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Endoplasmic Reticulum
(drug effects, pathology)
- Gene Deletion
- Leukemia L1210
(drug therapy, pathology)
- Mice
- Microtubule-Associated Proteins
(metabolism)
- Photochemotherapy
(adverse effects)
- Photosensitizing Agents
(pharmacology)
- Porphyrins
(pharmacology)
- Proto-Oncogene Proteins c-bcl-2
(antagonists & inhibitors, deficiency, metabolism)
- Time Factors
|
