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)

Loss of p53 function by inactivating mutations results in abrogation of NO*induced apoptosis in human lymphoblastoid cells. Here we report characterization of apoptotic signaling pathways activated by NO* in these cells by cDNA microarray expression and immunoblotting. A p53-mediated transcriptional response to NO* was observed in p53-wild-type TK6, but not in closely related p53-mutant WTK1, cells. Several previously characterized p53 target genes were up-regulated transcriptionally in TK6 cells, including phosphatase PPM1D (WIP1), oxidoreductase homolog PIG3, death receptor TNFRSF6 (Fas/CD95), and BH3-only proteins BBC3 (PUMA) and PMAIP1 (NOXA). NO* also modulated levels of several gene products in the mitochondria-dependent and death-receptor-mediated apoptotic pathways. Inhibitors of apoptosis proteins X-chromosome-linked inhibitor of apoptosis, cellular inhibitor of apoptosis protein-1, and survivin were significantly down-regulated in TK6 cells, but not in WTK1 cells. Smac release from mitochondria was induced in both cell types, but release of apoptosis-inducing factor and endonuclease G was detected only in TK6 cells. Fas/CD95 was increased, and levels of the antiapoptotic proteins Bcl-2 and Bcl-x/L were reduced in TK6 cells. Activation of procaspases 3, 8, 9, and 10, as well as Bid and poly(ADP-ribose) polymerase cleavage, were observed only in TK6 cells. NO* treatment did not alter levels of death receptors 4 and 5, Fas-associated death domain or proapoptotic Bax and Bak proteins in either cell line. Collectively, these data show that NO* exposure activated a complex network of responses leading to p53-dependent apoptosis via both mitochondrial and Fas receptor pathways, which were abrogated in the presence of mutant p53.
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PMID:Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. 1512 37

The mannosylated lipoarabinomanan (ManLAM) from mycobacterial species possesses strong anti-apoptotic action. Here we examined the ability of ManLAM isolated from Mycobacterium tuberculosis H37Rv to alter expression profiles of apoptosis-related genes in mouse macrophages infected with Mycobacterium bovis BCG Danish strain. ManLAM suppressed BCG-induced apoptosis and activities of caspase-1, -3, -8 and 9. Mouse Apoptosis Gene Array showed that ManLAM significantly down-regulated pro-apoptotic and proinflammatory genes: caspase-1, -3, -7, -8 and -9, TNF-alpha/TNFSF2, Fas/TNFRSF6, Bax-alpha, as well as IL-12 p35 and iNOS simultaneously up-regulating anti-apoptotic genes such as Bcl-2 and Mcl-1. The effect of ManLAM was contrary to BCG-induced up-regulation of proapoptotic and pro-inflammatory genes and consistent with the functional data.
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PMID:Gene expression profiling of lipoarabinomannan-treated mouse macrophage cultures infected with Mycobacterium bovis BCG. 1864

Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer.
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PMID:A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells. 2379 33