Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD20 is a B-cell differentiation antigen and known to induce apoptosis in Burkitt's lymphoma/leukemia (BL) cells upon antibody-mediated crosslinking. We examined the biological effect of CD20 crosslinking on BL cell lines and observed that apoptosis induction is accompanied by activation of multiple caspases, including caspase-8, -9, -3, -2, and -7. Further investigation revealed a clear synergism between apoptosis mediated by CD20 and by B-cell antigen receptor (BCR). Examination of the effect of simultaneous crosslinking of other cell surface molecules with crosslinking of CD20 or BCR on apoptosis induction showed that these molecules had either a synergistic or inhibitory effect on induction of apoptosis. It is worth noting that some molecules had a different effect on CD20- and BCR-mediated apoptosis. Simultaneous crosslinking of the molecules CD10, CD22, CD72, and CD80 inhibited BCR-mediated apoptosis, but enhanced CD20-mediated apoptosis. Further studies revealed that regulation of CD20-induced apoptosis by other costimulatory molecules is achieved by modification of caspase activation. CD20-mediated apoptosis in BL cells may provide not only a model for understanding the mechanism regulating clonal selection of B cells but a new therapeutic strategy for BL patients.
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PMID:Costimulatory signals distinctively affect CD20- and B-cell-antigen-receptor-mediated apoptosis in Burkitt's lymphoma/leukemia cells. 1276 85

Perturbations of B cells in HIV-infected individuals are associated with the overrepresentation of distinct B cell populations. Here we describe high extrinsic CD95 ligand (CD95L)-mediated apoptosis in CD10-/CD21lo mature/activated B cells that likely arise from HIV-induced immune activation. In addition, high intrinsic apoptosis was observed in CD10+ immature/transitional B cells that likely arise as a result of HIV-induced lymphopenia. CD10+ B cells expressed low levels of Bcl-2 and Bcl-xL, consistent with their high susceptibility to intrinsic apoptosis. Higher levels of activated Bax and Bak were induced in CD10+ B cells compared with CD95L-treated CD10- B cells, consistent with the greater involvement of mitochondria in intrinsic vs. extrinsic apoptosis. Of interest, both extrinsic apoptosis in CD95L-treated CD10- B cells and intrinsic apoptosis in CD10+ B cells were associated with caspase-8 activation. Our data suggest that two distinct mechanisms of apoptosis are associated with B cells of HIV-infected individuals, and both may contribute to the depletion and dysfunction of B cells in these individuals.
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PMID:Two overrepresented B cell populations in HIV-infected individuals undergo apoptosis by different mechanisms. 1715 96

Matrix metalloproteinase 9 (MMP-9) is a Zn(2+)-dependent endopeptidase that degrades some of the components of basement membranes and extracellular matrix and thus participates in leukocyte infiltration during inflammation. In a model of zymosan peritonitis, neutrophil infiltration in MMP-deficient (MMP-9(-/-)) mice was significantly weaker at the time of their maximal influx in wild-type mice (6h). However, during the late stages of peritonitis (24h) an extended accumulation of neutrophils was observed in MMP-9(-/-)versus the wild-type mice. Recently, we reported that the ratio of apoptosis of inflammatory leukocytes is impaired in MMP-9(-/-) mice during late peritonitis and the process depends on COX-1-driven PGE(2). Here we scrutinized the alterations in apoptotic mechanisms by comparisons between MMP-9(-/-) and the wild-type mice. Altered apoptosis occurred only during late (24h) peritonitis and concerned only neutrophils, and not macrophages, mast cells or lymphocytes. Furthermore, expression and activity of caspases was altered in MMP-9(-/-) animals, delayed for caspase-8 and -9, and decreased in the case of caspase-3. Also the expression of Bax/Bcl-2 proteins was changed in MMP-9(-/-) mice. These changes, and in particular the impaired neutrophil apoptosis and weaker caspase-3 activity, were restored by the selective COX-1 inhibition. We conclude that in mice lacking MMP-9 the enhanced COX-1-PGE(2) decreases caspase-3 expression and activity leading to impaired apoptosis of inflammatory neutrophils resulting in abnormal accumulation of the cells at the inflammatory focus. The data also reinforce the notion that MMP-9 is a key enzyme in neutrophil biology.
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PMID:Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3. 1968 97