Caspase DNAase

Figure 20.35 Mechanisms by which external or internal stress leads to cell damage resulting in apoptosis. The stress leads to activation of initiator proteolytic enzymes (caspases) that initiate activation of effector caspases. These enzymes cause proteolytic damage to the cytoskeleton, plasma membrane and DNA. The activation of DNAases in the nucleus results in cleavage of DNA chains between histones that produces a specific pattern of DNA damage which, upon electrophoresis, gives a specific pattern of DNA fragments. The major endproduct of apoptosis are the apoptolic bodies which are removed by the phagocytes.

DNAase inhibitor ICAD (inhibitor of caspase-activated DNAase) Inhibitor of a DNAase responsible for DNA fragmentation (Enari et al, 1998). 

Endonucleases. Endonucleases provide for DNA cleavage into small ( 200 base pairs) fragments, which is an essential step in apoptotic cascade (Wyllie 1980 Wyllie 1998). Endonucleases are stimulated by Ca2+ and their activation was detected in several cell types undergoing apoptosis (McConkey et al., 1988 Aw et al., 1990). The intimate mechanisms of endonucleases action remain not fully described at least in part they can be explained through the involvement of caspase-3 activated endonuclease (or caspase-activated DNAase - (Enari et al., 1998)). Nonetheless, the chromatin fragmentation was also observed in cell (and caspase)-free system, when isolated nuclei were treated with Ca2+ and ATP, suggesting the existence of caspase-independent DNA cleavage mechanism (Jones et al., 1989). 

DNAase inhibitor ICAD (inhibitor of caspase-activated DNAase)... 

Mitochondria and Apoptosis The loss of mitochondrial integrity is a major route initiating apoptosis (see Chapter 18, section V). The intermembrane space contains procaspases —2, —3, and 9, which are proteolytic enzymes that are in the zymogen form (i.e., must be proteolytically cleaved to be active). It also contains apoptosis initiating factor (AIF) and caspase-activated DNAase (CAD). Cytochrome c, which is loosely bound to the outer mitochondrial membrane, may also enter the intermembrane space when the electrochemical potential gradient is lost. The release of cytochrome c and the other proteins into the cytosol initiates apoptosis. 

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