Photodynamic triggering of calcium oscillation in the isolated rat pancreatic acini

Abstract

Photodynamic agents, due to their photon‐dependent selective activation, can selectively activate a number of physiological processes and may directly modulate signal transduction in a number of cells including pancreatic acinar cells. Activation of the photodynamic agent sulphonated aluminium phthalocyanine (SALPC) triggered recurrent cytosolic calcium ([Ca2+]i) spiking in pancreatic acinar cells. The photodynamically triggered calcium spiking could be blocked by phosphatidylinositol‐specific phospholipase C (PI‐PLC) inhibitor U73122, but not by phosphatidylcholine‐specific phospholipase C inhibitor D609. Removal of extracellular Ca2+ abolished spiking, as did 2‐aminoethoxydiphenylborate (2‐APB), an inhibitory modulator of IP3‐mediated Ca2+ release from intracellular stores. These data suggest that SALPC photodynamic action may permanently fix PI‐PLC in an active conformation, and this produced recurrent [Ca2+]i spiking.

Intracellular signaling mechanisms in photodynamic therapy

“…Accordingly, the [Ca 2 + ] i oscillations induced by photosensitization of rat pancreatic acini were inhibited by U73122, an inhibitor of the phosphatidylinositol-4,5-bisphosphate-specific phospholipase C (PI-PLC), and this mechanism was also involved in the transient [Ca 2 + ] i increase observed in the mouse L5178Y lymphoma cells, sensitized with AlPc [107,120]. In contrast, D609, which inhibits the phosphatidylcholine-specific phospholipase C, had no effect on the [Ca 2 + ] i response in sensitized rat pancreatic acini [107]. The [Ca 2 + ] i oscillations induced by photosensitization of pancreatic acinar cells with sulfonated aluminum phthalocyanine were inhibited by an antagonist of the cholecystokinin receptors [117], indicating that the photodynamic In human adenocarcinoma HeLa cells photosensitized with verteporfin the release of Ca 2 + from internal stores, mainly from the ER, was associated with a rapid caspaseindependent depletion of sarco/endoplasmic reticulum Ca 2 + ATPase (SERCA2) [112].…”

“…However, the [Ca 2 + ] i response in human fibroblasts sensitized with tetrasulfonated aluminum phthalocyanine (AlPcS 4 ) was mainly due to Ca 2 + influx when low fluence rates were used, and to the release from internal stores at higher light doses [104]. The release of Ca 2 + from internal stores, through the inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) receptor, was shown to mediate the oscillatory pattern of the [Ca 2 + ] i response in isolated rat pancreatic acini sensitized with gadolinium porphyrinlike macrocycle B [106] or AlPcS 4 [107]. Accordingly, the [Ca 2 + ] i oscillations induced by photosensitization of rat pancreatic acini were inhibited by U73122, an inhibitor of the phosphatidylinositol-4,5-bisphosphate-specific phospholipase C (PI-PLC), and this mechanism was also involved in the transient [Ca 2 + ] i increase observed in the mouse L5178Y lymphoma cells, sensitized with AlPc [107,120].…”

“…However, in some cell types it was observed that elevation of the [Ca 2 + ] i following photosensitization promotes cell survival and buffering of the intracellular Ca 2 + enhanced cell death [104,108,119]. The [Ca 2 + ] i rise upon photosensitization may originate from the influx of Ca 2 + through ion channels [108,116], release of Ca 2 + sequestered in internal stores, including the ER and possibly the mitochondria [104,106,107,112,120], and/or activation of ion exchange mechanisms [111] (Fig. 2).…”

“…The release of Ca 2 + from internal stores, through the inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) receptor, was shown to mediate the oscillatory pattern of the [Ca 2 + ] i response in isolated rat pancreatic acini sensitized with gadolinium porphyrinlike macrocycle B [106] or AlPcS 4 [107]. Accordingly, the [Ca 2 + ] i oscillations induced by photosensitization of rat pancreatic acini were inhibited by U73122, an inhibitor of the phosphatidylinositol-4,5-bisphosphate-specific phospholipase C (PI-PLC), and this mechanism was also involved in the transient [Ca 2 + ] i increase observed in the mouse L5178Y lymphoma cells, sensitized with AlPc [107,120]. In contrast, D609, which inhibits the phosphatidylcholine-specific phospholipase C, had no effect on the [Ca 2 + ] i response in sensitized rat pancreatic acini [107].…”

“…Photosensitization of the mouse lymphoma L5178Y cells with AlPc leads to a rapid accumulation of Ins(1,4,5)P 3 and increases the [Ca 2 + ] i , mainly due to release from internal stores, and both events are significantly reduced by the phosphatidylinositol-specific phospholipase C inhibitor U73122 [120]. This phospholipase C inhibitor also inhibits [Ca 2 + ] i spicking in rat pancreatic acini sensitized with AlPcS 4 [107]. The mechanism of PI-PLC activation in PDT remains to be determined, but it may be secondary to a small rise in the [Ca 2 + ] i since the enzyme is activated by Ca 2 + [131].…”