Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caspase-3 initiates apoptotic DNA fragmentation by proteolytically inactivating DFF45 (DNA fragmentation factor-45)/ICAD (inhibitor of caspase-activated DNase), which releases active DFF40/CAD (caspase-activated DNase), the inhibitor's associated endonuclease. Here, we examined whether other apoptotic proteinases initiated DNA fragmentation via DFF45/ICAD inactivation. In a cell-free assay, caspases-3, -6, -7, -8, and granzyme B initiated benzoyloxycarbonyl-Asp-Glu-Val-Asp (DEVD) cleaving caspase activity, DFF45/ICAD inactivation, and DNA fragmentation, but calpain and cathepsin D failed to initiate these events. Strikingly, only the DEVD cleaving caspases, caspase-3 and caspase-7, inactivated DFF45/ICAD and promoted DNA fragmentation in an in vitro DFF40/CAD assay, suggesting that granzyme B, caspase-6, and caspase-8 promote DFF45/ICAD inactivation and DNA fragmentation indirectly by activating caspase-3 and/or caspase-7. In vitro, however, caspase-3 inactivated DFF45/ICAD and promoted DNA fragmentation more effectively than caspase-7 and endogenous levels of caspase-7 failed to inactivate DFF45/ICAD in caspase-3 null MCF7 cells and extracts. Together, these data suggest that caspase-3 is the primary inactivator of DFF45/ICAD and therefore the primary activator of apoptotic DNA fragmentation.
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PMID:Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. 1052 51

Acrolein is a highly reactive alpha,beta-unsaturated aldehyde, which is a product of lipid peroxidation. It is an environmental pollutant that has been implicated in multiple respiratory diseases. Acrolein is produced by the enzymatic oxidative deamination of spermine by amine oxidase. Oxidation products of polyamines have been involved in the inhibition of cell proliferation, apoptosis, and the inhibition of DNA and protein synthesis. The present study investigates the mechanism of cell death induced by acrolein. Acrolein induced apoptosis through a decrease in mitochondrial membrane potential, the liberation of cytochrome c, the activation of initiator caspase-9, and the activation of the effector caspase-7. However, acrolein inhibited enzymatic activity of the effector caspase-3, although a cleavage of pro-caspase-3 occurred. The activation of caspases-9 and -7 was confirmed by the cleavage of their pro-enzyme form by acrolein. Apoptosis was inhibited by an inhibitor of caspase-9, but not by an inhibitor of caspase-3. The induction of apoptosis by acrolein was confirmed morphologically by the condensation of nuclear chromatin and by the cleavage of the inhibitor of caspase activated DNase (ICAD), which leads to the liberation of CAD that causes DNA fragmentation. These results demonstrate that acrolein causes apoptosis through the mitochondrial pathway.
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PMID:The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway. 1584 39