Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.
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PMID:Apoptotic signaling pathway activated by Helicobacter pylori infection and increase of apoptosis-inducing activity under serum-starved conditions. 1129 39

Apoptosis induction of host macrophages has emerged as a common virulence mechanism among bacterial pathogens. Infection with Campylobacter jejuni is a leading cause of gastroenteritis worldwide and is characterized by an acute inflammatory response in the small intestine. The authors used the human monocytic cell line THP-1 to examine apoptosis induction and pro-inflammatory cytokine production during C. jejuni infection. Flow cytometric analysis revealed that 48 h after inoculation, a C. jejuni wild-type isolate induced apoptosis in 63 % of THP-1 cells while only 34 % of cells inoculated with a ciaB mutant, which does not secrete the Cia (Campylobacter invasion antigens) proteins, underwent apoptosis. Complementation of the ciaB mutant resulted in levels of apoptosis similar to those induced by the C. jejuni wild-type isolate, suggesting that the Cia proteins have a role in apoptosis induction. It was shown that a proteinase K- and heat-stable component of C. jejuni also stimulated THP-1 apoptosis. Inoculation with a C. jejuni gmhD mutant indicated that lipooligosaccharide was not the stimulatory molecule. Immunoblot and ELISA analyses revealed that C. jejuni infection stimulated the synthesis, processing and secretion of interleukin 1 beta (IL-1 beta). Inhibition of caspase 1 activity eliminated IL-1 beta processing and secretion, but did not affect apoptosis induction. In addition, treatment of cells with a caspase-9-specific inhibitor did not affect apoptosis induction, arguing against activation of an apoptotic pathway dependent on either caspase 1 or 9 activation. Collectively, these data suggest that the inoculation of macrophages with C. jejuni results in the processing of IL-1 beta and apoptosis through different regulatory pathways. Furthermore, these data argue that C. jejuni may use a mechanism distinct from Salmonella typhimurium and Shigella flexneri to initiate macrophage apoptosis and release of IL-1 beta.
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PMID:Campylobacter jejuni infection of differentiated THP-1 macrophages results in interleukin 1 beta release and caspase-1-independent apoptosis. 1499 5

In previous studies, parasporin-2Aa1, originally isolated from Bacillus thuringiensis strain A1547, was shown to be cytotoxic against specific human cancer cells but the mechanisms of action were not studied. In the present study, we found that proteinase K activated parasporin-2Aa1 protein isolated from a novel B. thuringiensis strain, 4R2, was specifically cytotoxic to endometrial, colon, liver, cervix, breast and prostate cancer. It showed no toxicity against normal cells. Upon treatment with proteinase K-activated parasporin-2Aa1, morphological changes were observed and western blot analysis revealed the cleavage of poly (ADP-Ribose) polymerase, caspase-3 and caspase-9 in cancer cell lines exclusively, indicative of programmed cell death, apoptosis. Flow cytometry analyses,using propidium iodide and annexin V, as well as a caspases 3/7 assay confirmed apoptosis induction. Further analyses were performed to study survival pathways, including AKT, XIAP, ERK1/2 and PAR-4, a known inducer of apoptosis. These results indicate that parasporin-2Aa1 is a selective cytotoxic protein that induces apoptosis in various human cancer cell lines from diverse tissues.
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PMID:Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells. 2626 2