The P2X7 receptor is an ATP gated ion channel, that is endowed with a strong pro-apoptotic activity but also promotes cell survival in the absence of serum. While the pro-apoptotic and pro-necrotic activity of the receptor has been widely investigated, little is known about its growth promoting function. In the last years we focused our attention on the organellar network, fundamental for both cell survival and death, studying the behavior of mitochondria and endoplasmic reticulum (ER) in HEK cells expressing the P2X7 receptor. Thanks to targeted calcium sensing probes we were able to measure increased mitochondrial calcium levels and enhanced reticular calcium uptake in receptor transfected cells versus mock. Experiments with thapsigargin on cell populations allowed us to estimate a total content of reticular calcium significantly higher for P2X7 transfectants. P2X7 expressing clones also resulted more sensitive to carbachol stimulation that caused a burst in both reticular and mitochondrial calcium levels. This organellar calcium increase correlated with longer survival in the absence of serum and enhanced ATP production. These data allow us to propose a model in which P2X7 expression will determine an increased cellular calcium influx that will be stored in both mitochondria ad ER causing on one hand an higher energy production and on the other stimulating the proliferative pathways involving a release of calcium from the endoplasmic reticulum.
P2X7 receptor mediated proliferation: a mitochondrial-reticular explanation
CALLEGARI, Maria Giulia;PINTON, Paolo;RIZZUTO, Rosario;DI VIRGILIO, Francesco;ADINOLFI, Elena
2006
Abstract
The P2X7 receptor is an ATP gated ion channel, that is endowed with a strong pro-apoptotic activity but also promotes cell survival in the absence of serum. While the pro-apoptotic and pro-necrotic activity of the receptor has been widely investigated, little is known about its growth promoting function. In the last years we focused our attention on the organellar network, fundamental for both cell survival and death, studying the behavior of mitochondria and endoplasmic reticulum (ER) in HEK cells expressing the P2X7 receptor. Thanks to targeted calcium sensing probes we were able to measure increased mitochondrial calcium levels and enhanced reticular calcium uptake in receptor transfected cells versus mock. Experiments with thapsigargin on cell populations allowed us to estimate a total content of reticular calcium significantly higher for P2X7 transfectants. P2X7 expressing clones also resulted more sensitive to carbachol stimulation that caused a burst in both reticular and mitochondrial calcium levels. This organellar calcium increase correlated with longer survival in the absence of serum and enhanced ATP production. These data allow us to propose a model in which P2X7 expression will determine an increased cellular calcium influx that will be stored in both mitochondria ad ER causing on one hand an higher energy production and on the other stimulating the proliferative pathways involving a release of calcium from the endoplasmic reticulum.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
