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

被引:76
作者
Rosado, Juan A. [1 ]
Lopez, Jose J.
Gomez-Arteta, Emilio
Redondo, Pedro C.
Salido, Gines M.
Pariente, Jose A.
机构
[1] Univ Extremadura, Dept Physiol, Cellular Physiol Res Grp, Caceres 10071, Spain
[2] Hosp San Pedro de Alcantara, Caceres, Spain
关键词
D O I
10.1002/jcp.20715
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 pp60(src), 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.
引用
收藏
页码:142 / 152
页数:11
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