Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) plays an import role in the control of apoptosis. The most well known apoptotic pathway regulated by TNF involves the TNFR1-associated death domain protein, Fas-associated death domain protein, and caspase-8. This study examines the mechanism of TNF-induced apoptosis in FaO rat hepatoma cells. TNF treatment significantly increased the percentage of apoptotic cells. TNF did not activate caspase-8 but activated caspase-3, -10, and -12. The effect of TNF on the expression of different members of the Bcl-2 family in these cells was studied. We observed no detectable changes in the steady-state levels of Bcl-X(L), Bax, and Bid, although TNF suppresses Bcl-2 expression. Dantrolene suppressed the inhibitory effect of TNF on Bcl-2 expression. TNF induced release of Ca(2+) from the endoplasmic reticulum (ER) that was blocked by dantrolene. Importantly, the expression of Bcl-2 blocked TNF-induced apoptosis and decreased TNF-induced Ca(2+) release. These results suggest that TNF induces apoptosis by a mechanism that involves increasing Ca(2+) release from the ER and suppression of Bcl-2 expression.
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PMID:Tumor necrosis factor induces apoptosis in hepatoma cells by increasing Ca(2+) release from the endoplasmic reticulum and suppressing Bcl-2 expression. 1207 31

The pathway of interferon-gamma (IFN-gamma)-induced suppression in tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells (FLS) was investigated. rTRAIL triggered FLS apoptosis in a type II cell death manner, whereas IFN-gamma pretreatment significantly inhibited TRAIL-mediated apoptosis. As disruption of mitochondrial transmembrane potential (DeltaPsim), Leu-Glu-His-Asp ase (IETD ase) activity, and the appearance of hypodiploid DNA + cells were markedly suppressed in IFN-gamma-treated FLS in response to TRAIL, IFN-gamma-induced suppression was supposed to achieve at upstream of caspase-8. IFN-gamma rapidly phosphorylated signal transducers and activators of transcription 1 (STAT1), STAT3, and STAT6 as well as ERK, whereas enhanced neither phosphorylation of Akt nor nuclear translocation of nuclear factor kappaB (NF-kappaB) p65. Janus kinase (JAK)-induced phosphorylation of STAT1/3/6, which acts at translational regulation, seemed to be crucial because chemical inhibition of JAK as well as cycloheximide (CHX) abolished both the phosphorylation of STAT1/3/6 and the IFN-gamma-induced inhibitory effect. Although ERK was phosphorylated through IFN-gamma, chemical inhibition of ERK by PD98059 did not abolish the IFN-gamma-induced inhibitory effect. The authors tried to determine the responsible molecules; however, expression of TRAIL receptors; pro-caspase-3/-8/-9; Fas-associated death domain protein (FADD); tumor necrosis factor receptor 1-associated death domain protein (TRADD); silencer of death domain (SODD); FLICE inhibitory protein (FLIP); and Bcl-2, Bcl-xL, and Bax in FLS was not modulated by IFN-gamma. Although the authors have not yet clarified the precise mechanism, these data suggest that IFN-gamma/JAK/STAT pathway, which is supposed to be activated in inflammatory rheumatoid arthritis (RA) synovial tissues, contributes to form apoptosis resistance phenotype of the cells in situ, leading to a marked increase in cellularity of synovial cells.
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PMID:Significant inhibition of TRAIL-mediated fibroblast-like synovial cell apoptosis by IFN-gamma through JAK/STAT pathway by translational regulation. 1658 46

Human COLO 205 colon adenocarcinoma cells are immune to extrinsic apoptosis induced by immunomodulatory cytokines. Among the antiapoptotic mechanisms responsible for the immune escape, the overexpression of the cFLIP protein seems to be critical. cFLIP appears to inhibit the TNF-alpha-induced death receptor signal. The application of the metabolic inhibitor bisindolylmaleimide IX (Bis-IX), known as a potent PKC repressor, sensitized COLO 205 cells to TNF-alpha-mediated apoptosis. The Western-blot analysis revealed that the susceptibility of human COLO 205 cells to apoptogenic stimuli resulted from time-dependent reduction in cFLIP(L) and TRADD protein levels. At the same time, the level of FADD protein was up-regulated. Additionally, the combined TNF-alpha and Bis-IX treatment caused cleavages of Bid and procaspase-9, as well as cytochrome c release. Thus, the evidence of this study indicates that Bis-IX facilitates the death receptor signal mediated by TNF-R1. Moreover, Bis-IX alone initiated intrinsic apoptosis, which could be abolished by Bcl-2 delivery. It heralds the involvement of mitochondria in caspase-8-independent intrinsic apoptosis. In turn, the treatment with bisindolylmaleimide III (Bis-III) did not assist TNF-alpha-dependent apoptosis.
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PMID:Bisindolylmaleimide IX facilitates extrinsic and initiates intrinsic apoptosis in TNF-alpha-resistant human colon adenocarcinoma COLO 205 cells. 1834 86