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)

Mouse thymocytes are known to undergo apoptosis by ligating some unique anti-Thy-1 monoclonal antibodies (mAbs), G7 and KT16. However, the precise mechanisms of Thy-1-mediated apoptosis are as yet unclear. We investigated Thy-1-mediated apoptosis using our previously generated anti-Thy-1 mAb, MCS-34, which was similar to G7 because both antibodies recognized both Thy-1.1 and Thy-1.2 and bound Thy-1A epitope. Unlike G7, MCS-34 alone could not induce apoptosis in thymocytes; however, it could induce apoptosis when it was cross-linked with second antibodies. Thus, MCS-34 could not aggregate by itself, but G7 could. In the course of investigating the apoptosis-related molecules that were involved in the thymocyte apoptosis induced by cross-linking of MCS-34 or by G7 ligation, we found that CPP 32-like proteases were activated during the apoptosis. Furthermore, the expression of bcl-2 and bcl-XL proteins was decreased in these apoptosis processes. Whereas the ligation of MCS-34 alone could not generate apoptosis signals that led to the activation of CPP32-like proteases and the decrease in bcl-2 and bcl-XL expression, the aggregation of Thy-1 glycoprotein might be crucial to signal thymocyte apoptosis. These results indicate that MCS-34 is a useful anti-Thy-1 mAb for analyzing the Thy-1-mediated signals since MCS-34 can control the level of apoptosis by using second antibodies.
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PMID:Aggregation of Thy-1 glycoprotein induces thymocyte apoptosis through activation of CPP32-like proteases. 916 18

The purpose of the present study was to investigate the anti-proliferative and apoptotic effects of MCS-C2, a novel synthetic analogue of the pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human promyelocytic leukemia (HL-60) cells. When treated with 5 microM MCS-C2, inhibited proliferation associated with apoptotic induction was found in the HL-60 cells in a concentration-dependent and time-dependent manner, plus nuclear DAPI staining revealed the typical nuclear features of apoptosis. However, MCS-C2 showed almost no antiproliferative effect and no apoptotic induction in normal lymphocyte cells used as a control when compared with those in HL-60 cancer cells. Moreover, a flow cytometric analysis of the HL-60 cells using FITC-dUTP and propidium iodide (PI) showed that the apoptotic cell population increased gradually from <1% at 0 h to 34% at 12 h after exposure to 5 microM MCS-C2. This apoptotic induction was associated with the cleavage of Bid and a release of cytochrome c from mitochondria into the cytosol, followed by the activation of caspase-3 and inactivation of poly(ADP-ribose) polymerase (PARP). However, there was no significant change in any other mitochondrial membrane proteins, such as Bcl-2 and Bax. Consequently, the current findings suggest that the mitochondrial pathway was primarily involved in the MCS-C2-induced apoptosis in the human promyelocytic leukemia HL-60 cells.
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PMID:Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c release. 1589 58