Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium is involved in several steps of the apoptotic process. In nuclei, endonucleases are presumed to be the main targets of calcium; however, little is known about its role during the cytosolic phase of apoptosis. We used a cell-free system to address this question. Our results show that CaCl2 triggered nuclear apoptosis (i.e. typical morphological change and DNA fragmentation) at concentrations of 5 mM. This concentration was lowered 10-fold by the co-incubation with cytosolic extracts from nonapoptotic cells. Apoptotic changes induced by the incubation of nuclei with CaCl2 in the presence of these cytosols were strongly reduced in the presence of an inhibitor of caspase-3 and to a lesser extent by an inhibitor of caspase-1. We also show that calcium-induced apoptosis is affected by protease inhibitors such as N-tosyl-L-phenylalanine chloromethyl ketone, but not by calpain or several lysosomal protease inhibitors. The addition of CaCl2 to the cell-free system increased a caspase-3 activity in nonapoptotic cytosols as shown by specific antibodies and an enzymatic assay. No activation of a caspase-3-like activity by the addition of cytochrome c was observed in these extracts under similar conditions. The enhanced caspase-3 activity induced by calcium was inhibited by protease inhibitors affecting morphological nuclear apoptosis except for those responsible for the degradation of lamin A. These results suggest that CaCl2 could trigger, in normal cells, an apoptotic cascade through the activation of cytosolic caspase-3 activity.
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PMID:Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. 965 49

The role of intracellular Ca2+ homeostasis in mechanisms of neuronal cell death and cysteine protease activation was investigated in SH-SY5Y human neuroblastoma cells. Cells were incubated in 2 mM EGTA to lower intracellular Ca2+ or 5 mM CaCl2 to raise it. Cell death and activation of calpain and caspase-3 were measured. Both EGTA and excess CaCl2 elicited cell death. EGTA induced DNA laddering and an increase in caspase-3-like, but not calpain, activity. Pan-caspase inhibitors protected against EGTA-, but not CaCl2-, induced cell death. Conversely, excess Ca2+ elicited necrosis and activated calpain but not caspase-3. Calpain inhibitors did not preserve cell viability. Ca2+ was the death-mediating factor, because restoration of extracellular Ca2+ protected against cell death induced by EGTA and blockade of Ca2+ channels by Ni2+ protected against that induced by high Ca2+. We conclude that the EGTA treatment lowered intracellular Ca2+ and elicited caspase-3-like protease activity, which led to apoptosis. Conversely, excess extracellular Ca2+ entered Ca2+ channels and increased intracellular Ca2+ leading to calpain activation and necrosis. The mode of cell death and protease activation in response to changing Ca2+ were selective and mutually exclusive, demonstrating that these are useful models to individually investigate apoptosis and necrosis.
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PMID:Alterations of extracellular calcium elicit selective modes of cell death and protease activation in SH-SY5Y human neuroblastoma cells. 1021 61

Postmortem tenderization is induced by the cooperation of various related enzymes. In this study, CaCl2 and MDL-28170 (Cbz-Val-Phe-H, a calpain inhibitor) were used to regulate the postmortem tenderization process of duck breast muscle. Then the relationship between muscle tenderness change and different enzymes was investigated. At day 0, day 1, and day 4 of the postmortem ageing, the shear force, myofibril fragmentation index (MFI), enzymatic activities of calpains, cathepsin-B, caspase-3, Na+/K+-ATPase, and Ca2+-ATPase were respectively determined. The results showed that duck muscle tenderness could be significantly raised by CaCl2 and reduced by MDL-28170, respectively (P < 0.05). The CaCl2 treatment did not promote the calpains activity as predicted (P > 0.05), but significantly up-regulated the activity of cathepsin-B (P < 0.05). The MDL-28170 significantly inhibited the activity of the calpain system at day 1 (P < 0.05) and raised the activities of the selected 3 apoptosis-related enzymes, including caspase-3, Na+/K+-ATPase, and Ca2+-ATPase, at both day 1 and day 4 (P < 0.05). These data indicated that in duck, the calpain system could be well activated after death, and cathepsin-B might also play an important role in postmortem muscle tenderization. The caspase-3, Na+/K+-ATPase, and Ca2+-ATPase probably have no significant effects on duck muscle tenderness. It might provide useful information for duck production and further research on postmortem muscle tenderization.
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PMID:Investigation of the relationships between different enzymes and postmortem duck muscle tenderization. 3119 38