Intracellular calcium release is required for caspase-3 and -9 activation.
Increase in intracellular Ca2+ [Ca2+]i regulates many biological functions including apoptosis, but the protein(s) linking [Ca2+]i and apoptosis are not completely understood. We have previously shown that IP3R-deficient cells are resistant to T-cell receptor (TCR)-induced apoptosis due to lack of Ca2+ release from endoplasmic reticulum (ER) and calcineurin activation. Here we show that caspase-9 and -3 are not activated in IP3R-deficient cells after TCR stimulation, consistent with the resistance of these cells to apoptosis. However, we also demonstrate that Bcl-2 expression in IP3R-deficient cells is comparable to control cells. Taken together, these results strongly suggest that IP3R-mediated Ca2+ release plays a critical role in regulating the activity of caspases-3 and -9 independent of Bcl-2.
Tantral
Lee
L
Vascular Biology Laboratory, Department of Medicine, St. Luke's Roosevelt Hospital Center, New York, NY 10025, USA.
Malathi
Krishnamurthy
K
Kohyama
Shinya
S
Silane
Michael
M
Berenstein
Alejandro
A
Jayaraman
Thottala
T
D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry; D020013:Calcium Signaling; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019169:Jurkat Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D002118:Calcium