Early caspase‐3 activation independent of apoptosis is required for cellular function

Abstract

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.

Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells

“…53 Furthermore, caspase-3 and other caspases are expressed in platelets and are important in platelet activation, aggregation, and other events necessary for thrombopoiesis. 35,[54][55][56] In the context of MkMP formation and the engagement of caspase-3, the involvement and importance of proteolytic caspase activity independent of cell death in the generation at endothelial microparticles is worth noting. 57 A more recent report shows that mechanical forces stimulate the generation of endothelial microparticles independent of canonical apoptosis, but requires the action of caspases.…”

Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

“…PS scrambling was determined by the method of Rosado et al [23]. Treated and control PRP as well as washed platelet suspension samples were transferred to equal volumes of ice-cold 1% (w/v) glutaraldehyde in HBS for 10 min, and then incubated in 0.6 mg/mL buffered aqueous solution of annexin V fluorescein isothiocyanate for 10 min.…”

TRPC3 Regulates Agonist-stimulated Ca2+ Mobilization by Mediating the Interaction between Type I Inositol 1,4,5-Trisphosphate Receptor, RACK1, and Orai1

“…Ca 2ϩ release by ATP or CCh was estimated using the integral of the rise in [Ca 2ϩ ] i for 3 min after the addition of the agonist (38). Ca 2ϩ entry was estimated using the integral of the rise in [Ca 2ϩ ] i for 2.5 min after addition of CaCl 2 (39). Ca 2ϩ entry was corrected by subtraction of the [Ca 2ϩ ] i elevation due to leakage of the indicator.…”