Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously.
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PMID:Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. 856 30

The lpr and gld genes have been shown to encode the Fas antigen deletion mutant and the Fas ligand (FasL) mutant, respectively. An MRL strain of mice bearing the gld gene was observed to spontaneously develop granulomatous arteritis, similar to that in mice bearing the lpr gene, indicating that arteritis in this strain is due to an inefficient Fas-FasL interaction resulting in an incapacity for Fas-mediated apoptosis. The arterial lesions in both strains were characterized by a remarkable perivascular accumulation of activated macrophages bearing Mac-2 antigen, following the infiltration of CD4+ cells, and this resulted in the destruction of the arterial wall. Almost all of these infiltrating cells were Fas-positive, as determined in MRL/gld mice. Macrophage colony-stimulating factor (M-CSF), which is present at increased levels in MRL/lpr mice, but not in MRL/Mp- +/+ (MRL/+) mice, induced the expression of Mac-2 antigen and Fas antigen on spleen adherent cells of MRL/+ mice. Moreover, continuous infusion of M-CSF into the peritoneal cavity of subcutis of MRL/+ mice induced the release of oxygen radicals of peritoneal macrophages or granuloma formation associated with the massive accumulation of Mac-2+ cells, respectively. These findings suggest that macrophages in these mice, which may be activated by M-CSF and may avoid Fas-mediated apoptosis, play a critical role as effector cells in the destruction of arterial wall.
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PMID:Role of macrophages in the development of arteritis in MRL strains of mice with a deficit in Fas-mediated apoptosis. 887 Jun 94

Studies of CD95 (APO-1/Fas), a member of the death receptor family, have revealed that it is involved in two primary CD95 apoptotic signaling pathways, one regulated by the large amount of active caspase-8 (type I) formed at the death-inducing signaling complex and the other by the apoptogenic activity of mitochondria (type II). To date, it is still unclear which pathway will be activated in response to an apoptotic insult. Here, we demonstrate that the antiapoptotic molecule galectin-3, which contains the four amino acid-anti-death-motif (NWGR) conserved in the BH1 domain of the Bcl-2 member proteins, is expressed only in type I cells. Transfection of galectin-3 cDNA into galectin-3 null cells (type II) resulted converting them to type I apoptotic phenotype. In addition, we show that galectin-3 is complexed with CD95 in vivo identifying galectin-3 as a novel CD95-binding partner that determines which of the CD95 apoptotic signaling pathways the cell will select.
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PMID:Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways. 1515 87