Proteolytic enzymes of the caspase family, which reside as latent precursors in most nucleated metazoan cells, are core effectors of apoptosis. Of them, the executioner caspases- 3 and -7 exist within the cytosol as inactive dimers and are activated by a process called dimerization. Caspase inhibition is looked upon as a promising approach for treating multiple diseases. Though caspases have be...

OBJECTIVE We investigated the activation of caspases 8, 9, 1, and 3 in human ejaculated spermatozoa to study main pathways of apoptosis. Potential functional impact of this phenomenon and possible activation mechanisms were examined by [1] subjecting cells to freezing and thawing, and [2] testing the dependence of caspase activity on membrane integrity. DESIGN Experimental study. SETTING An...

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six...

Apoptosis, programmed cell death, is a process involved in the development and maintenance of cell homeostasis in multicellular organisms. It is typically accompanied by the activation of a class of cysteine proteases called caspases. Apoptotic caspases are classified into the initiator caspases and the executioner caspases, according to the stage of their action in apoptotic processes. Althoug...

Myeloic cells express a peculiar surface receptor for extracellular ATP, called the P2Z/P2X7 purinoreceptor, which is involved in cell death signalling. Here, we investigated the role of caspases, a family of proteases implicated in apoptosis and the cytokine secretion. We observed that extracellular ATP induced the activation of multiple caspases including caspase-1, -3 and -8, and subsequent ...

Apoptosis in response to TRAIL or TNF requires the activation of initiator caspases, which then activate the effector caspases that dismantle cells and cause death. However, little is known about the dynamics and regulatory logic linking initiators and effectors. Using a combination of live-cell reporters, flow cytometry, and immunoblotting, we find that initiator caspases are active during the...

The unfolding of apoptosis involves the orchestrated proteolysis of hundreds of proteins, and to achieve efficacy the cell has evolved a three-step activation cascade. First, initiator caspases (caspases 8, 9, 10) are activated either by external death ligands triggering the formation of the death-inducing signaling complex (DISC; caspases 8 and 10) or by the release of cytochrome c from mitoch...

Apoptosis is co-ordinated by a family of cysteine proteases, the caspases, that dismantle the cell by targeting a panoply of proteins for limited proteolysis. The mammalian caspase family contains 14 members, a subset of which participates in apoptosis, with the remainder likely to be involved in the processing of pro-inflammatory cytokines. Apical caspase activation events are typically initia...