부산대학교 도서관

Photodynamic therapy (PDT) is clinically approved for the treatment of several types of cancer as well as age-related macular degeneration, the leading cause of blindness in the elderly. PDT using the photosensitizer verteporfin has been previously shown to induce rapid apoptosis via a mitochondrial-caspase activation pathway. The impact of PDT on other cell ular organelles such as the endoplasmic reticulum (ER) is undefined. The effect of PDT on intracellular Ca2+([Ca2+]i) in control and Bcl-2-overexpressing HeLa cells was assessed. A greater [Ca2+]itransient was observed for Bcl-2 overexpressing cells in response to PDT. The PDT-induced Ca2+release was due to the emptying of Ca2+from ER and possibly mitochondrial stores and was not due to an influx of Ca2+from the medium. For Bcl-2-transfected cells, the release of Ca2+was incomplete as determined by a further [Ca2+]itransient produced by the addition of the Ca2+ionophore ionomycin after PDT. Furthermore, extrusion of Ca2+was not hindered while ER-mediated sequestration of Ca2+was impaired after PDT. Impairment of ER-mediated sequestration of Ca2+may be due to the immediate caspase-independent depletion of sarco/endoplasmic reticulum Ca2+ATPase-2 (SERCA2) that occurred in response to PDT in birth HeLa/Neo and Bcl-2 overexpressed HeLa cells. In summary, PDT induced the rapid degradation of SERCA2 and release of ER and mitochondrial Ca2+stores. Although overexpression of Bcl-2 did not protect against SERCA2 degradation, it may influence the release of Ca2+from ER and mitochondrial stores in PDT-treated cells.