Early caspase-3 activation independent of apoptosis is required for cellular function.
A number of pro-apoptotic stimuli induce the activation of caspase-9, an initiator protease that activates executioner caspases, such as caspase-3, leading to the development of programmed cell death. Here we demonstrate that cell (platelets and pancreatic acinar cells) stimulation with agonists induces a bimodal activation of caspase-3. The early caspase-3 activation occurs within 1 min of stimulation and is independent on caspase-9 or mitochondrial cytochrome c release suggesting that is a non-apoptotic event. The ability of agonists to induce early activation of caspase-3 is similar to that observed for other physiological processes. Activation of caspase-3 by physiological concentrations of cellular agonists, including thrombin or CCK-8, is independent of rises in cytosolic calcium concentration but requires PKC activation, and is necessary for agonist-induced activation of the tyrosine kinases Btk and pp60src and for several cellular functions, including store-operated calcium entry, platelet aggregation, or pancreatic secretion. Thus, early activation of caspase-3 seems to be a non-apoptotic event required for cellular function.
Rosado
Juan A
JA
Department of Physiology (Cellular Physiology Research Group), University of Extremadura, Cáceres, Spain. jarosoda@unex.es
Lopez
Jose J
JJ
Gomez-Arteta
Emilio
E
Redondo
Pedro C
PC
Salido
Gines M
GM
Pariente
Jose A
JA
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology*; D010974:Platelet Aggregation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D010718:Phosphatidylserines; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D011493:Protein Kinase C; D013917:Thrombin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D012844:Sincalide; D002118:Calcium