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Biomedical subjects

E Hébert

Publications and source records attributed to E Hébert.

10 recordsLinked to original sources
PubMed2002

Efficacy of the non-peptide CGRP receptor antagonist BIBN4096BS in blocking CGRP-induced dilations in human and bovine cerebral arteries: potential implications in acute migraine treatment.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator in brain vessels and it has been implicated in the pathogenesis of migraine headache. Blocking post-junctional CGRP receptors, mediators of trigeminal-induced vasodilation, has been suggested as a potential antimigraine strategy. In this study, we tested the ability of a new non-peptide CGRP receptor antagonist, BIBN4096BS, to inhibit the CGRP-induced dilation in human and/or bovine brain vessels and compared it to that of the antagonist alpha-CGRP(8-37). BIBN4096BS and alpha-CGRP(8-37) both blocked the alpha-CGRP-induced dilation in bovine middle artery segments with respective potency (pK(B) values) of 6.3 and 7.8. In human pial vessels, BIBN4096BS was particularly potent. When tested at 10(-14)-10(-9) M concentrations, it induced a rightward shift in the alpha-CGRP concentration-response curve and yielded a biphasic Schild plot suggesting interaction with more than one receptor population, as was also indicated by the significant best fit of the alpha-CGRP-induced dilation in human brain vessels with a two receptor site interaction. Schild plot analysis in the linear portion of the BIBN4096BS inhibition curve revealed interaction with one high affinity site (pA(2) value approximately 14). In bovine vessels, both alpha-CGRP(8-37) and BIBN4096BS concentration-dependently reversed a pre-established CGRP-induced dilation ( approximately 59 and 85%, respectively), BIBN4096BS being approximately tenfold more potent than alpha-CGRP(8-37) (respective pIC(50) values of 7.5 and 6.75). In human middle cerebral and middle meningeal arteries, BIBN4096BS reversed the alpha-CGRP-induced dilation (> or =70%) by interaction with two different receptor populations: it exhibited a high affinity for one population (pIC(50) value approximately 13) and a lower affinity for the other (pIC(50) value approximately 8). The present data demonstrate that BIBN4096BS is a very potent antagonist that could, depending on its bioavailability and in vivo affinity, be of potential benefit in the acute treatment of migraine headache by blocking and/or reversing the CGRP-mediated dilation of intracranial vessels induced by activation of trigeminovascular afferents.

Acute Disease↗
PubMed2000

Endogenous lectins as cell surface transducers.

Interactions between cells or between cell and substratum involve specific receptors and their ligands. Among the various cell surface receptors identified during the last decades, the carbohydrate-binding proteins, e.g., lectins are of peculiar interest because glycolipids, glycoproteins and proteoglycans have been shown to interact with lectins on the surface of animal cells. Animal lectins are recognized as molecules playing important roles in a variety of biological processes through binding to glycoconjugates and lectin-like receptors such as selectins, sialoadhesins (CD22, CD33), natural killer receptors (NKR-P1, CD69 and CD94/NKG2), hyaluronate receptors (CD44, RHAMM, ICAM-1), B-cell associated antigen (CD23, CD72), beta2 leukocyte integrin (CD11b/CD18) or the well-known receptors for mannose, mannose-6-phosphate or asialoglycoprotein have been suggested to be able to mediate the transfer of information from the outside to the inside of the cell. This review focuses on the most recent advances in our understanding of the molecular basis of "outside-in" signaling mediated by lectins. Lectin-like receptors are involved in signal transduction in a great variety of ways; at the molecular level, they mimic in most of the cases the function of growth factor receptor either coupled to tyrosine kinase activity or to heterotrimeric G protein. They lead to a multiplicity of cellular events following their activation depending on factors such as cellular type, species and/or tissue. Nevertheless the potential of surface lectins as transducers is emphasized by the observation that in a few cases lectin-like receptors induce either novel signal transduction mechanism or new intracellular events with regards to what it has been observed as a consequence of growth factor receptor activation. This observation brings the idea that lectins may offer, as cell surface transducers, an alternative or additional signaling potential to cell.

Animals↗
PubMed1999

The tat protein of HIV-1 induces galectin-3 expression.

Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates. Galectin-3 is a beta-galactoside-binding lectin whose expression is associated with various pathological processes including human T lymphotropic virus (HTLV)-I-infection of human T cell lines and human immunodeficiency virus (HIV) infection of T-lymphoblastic Molt-3 cell line. In the case of HIV-infected cells, it has been suggested that the increase in galectin-3 expression could be related to the expression of the viral regulatory gene tat. These results prompt us to perform more extensive analyses of the relationship between galectin-3 and HIV-1 Tat expressions. In this study, we found that Tat protein expression induces an upregulation of galectin-3 in several human cell lines. In co-transfection experiments, the 5'-regulatory sequences of the galectin-3 gene were significantly upregulated by expression vectors encoding the Tat protein. Analysis performed with 5'-regulatory deleted sequences suggested that galectin-3 induction by Tat is dependent on activation of the Sp-1 binding transcription factor.

Animals↗
PubMed1997

Lack of modulation of the galectin-3 and asialoglycoprotein receptor transcription in hepatocarcinoma of transgenic mice.

Galectin-3 and asialoglycoprotein receptor are lectins belonging to the classes of soluble lectins and of membrane C type lectins respectively. Conflicting results have been reported concerning their transcription level in the time course development of tumours. In the present study we investigated the abnormalities and the transcription levels of galectin-3 and asialoglycoprotein receptor genes in liver-targeted SV40 large T transgenic mice related to normal mice. In the strain expressing the highest level of large T, 100% of the male mice reproducibly developed an hepatocarcinoma. We provide evidence that the galectin-3 and asialoglycoprotein receptor genes are stable in such mice. The galectin-3 gene is weakly transcribed and its level is identical and constant in normal and transgenic mice, suggesting a lack of involvement in the development of large T-induced hepatocarcinoma. The asialoglycoprotein receptor gene is actively transcribed and its level remains high all along the development of the tumour; therefore, in such an hepatocarcinoma the asialoglycoprotein receptor could be used to take up drugs, genes or oligonucleotides associated with glycosylated carriers bearing galactose residues in a terminal non-reducing position.

Animals↗
PubMed1996

Transformation but not ras-transfection increases the expression of galectin-3 in human HOS cells.

In ras-transfected NIH3T3 cells, the transcription of the Mr 34,000 beta-galactoside specific lectin galectin-3 depends on transformation phenotypes. This observation suggests that this lectin is associated with the transformation process and/or that the ras oncogene may modulate its expression; nevertheless the involvement of ras-gene product in galectin-3 gene expression still remains unclear. In the present study, we investigated the galectin-3 expression in human HOS cells transiently or stably transfected with a ras-containing vector. We observed an increase in galectin-3 mRNA and protein content in stably ras-transfected cells which had lost their anchorage dependence for growth but no increase in cells which needed anchorage for growth or in transiently ras-transfected cells. These results suggest that the galectin-3 up-regulation in ras-transfected HOS cells is the consequence of the cell transformation rather than a direct effect of the ras gene product on galectin-3 gene expression.

Adenocarcinoma↗
PubMed1994

Galectin-3 mRNA level depends on transformation phenotype in ras-transformed NIH 3T3 cells.

The increase in galectin-3 lectin content observed in tumours or in in vitro transformed cells suggests that this lectin is important in the transformation process. In the present study, we investigated the mRNA expression level of the galectin-3, galectin-1 and macrophage mannose receptor in normal and ras-transformed NIH 3T3 cells in relation to their transformation state. The galectin-3 mRNA content in ras-transformed cells is increased in fully transformed cells, with a maximum in ras-transformed cells that have lost their growth anchorage-dependence. Under the same conditions, the galectin-1 mRNA level which was high in normal cells, increased slightly in transformed cells. The mRNA for the macrophage mannose receptor was not detected in 3T3 cells or in their ras-transformed counterparts.

3T3 Cells↗
PubMed1994

Analysis of the IGF-II receptor gene copy number in breast carcinoma.

Insulin and the insulin-like growth factors (IGFs) may be important regulators of breast cancer growth. The IGF-II receptor is identical to the mannose 6-phosphate (Man-6-P) receptor, which is involved in lysosomal enzyme pathways. In order to determine whether the Man-6-P/IGF-II receptor gene copy number is altered in breast cancer we analysed specimens of invasive breast carcinoma from 51 patients by Southern blotting. No amplification of the receptor gene was observed whatever the clinical presentation of the tumour and irrespective of a concomitant amplification of c-erbB2 or int-2 genes in several tumours. As indicated by Northern blotting, the gene is transcribed in breast tumour tissues and non-tumour breast tissue. These results suggest that the receptor gene is stable in breast carcinoma and that, if anything, the receptor involvement in breast cancer progression may be the result of a disregulation of its expression at a post-transcriptional or post-translational level.

Adult↗
PubMed1993

Oncogenes and expression of endogenous lectins and glycoconjugates.

It is now well established that malignant transformation of eucaryotic cells is concomitant with typical alterations of glycosylation and the expression pattern of endogenous lectins. In parallel, oncogene transfection studies revealed a correlation between the expression of some of these genes, the transformed state and perhaps metastasis. These observations lead to the idea that oncogenes may control the expression of enzymes involved in the biosynthetic pathway of cell membrane glycoconjugates and the expression of endogenous lectins. Indeed, several contributions have shown that cells upon transfection with activated oncogenes of the ras family become invasive and/or metastatic and have their membrane glycoproteins modified. Information on the molecular mechanism of this postulated oncogene regulation is still lacking. Because of the diversity of the functions of oncogene-encoded proteins, further experiments dealing with other activated oncogenes may help in deciphering the regulation of expression of glycoconjugates and endogenous lectins together with their functions.

Animals↗
PubMed1984

Conformational changes induced in DNA by the in vitro reaction with the mutagenic amine: 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido (1,2-a: 3', 2'-d) imidazole.

The conformation of synthetic or natural DNAs modified in vitro by covalent binding of N-AcO-A-Glu-P-3 was investigated by fluorescence and circular dichroism. In all cases, substitution occurs mainly on the C8 of guanine residues. In modified poly(dG-dC).poly(dG-dC) or poly(dA-dC).poly(dG-dT) in B conformation, A-Glu-P-3 residues interact strongly with the bases whereas in Z conformation these residues are largely exposed to the solvent and interact weakly with the bases. A-Glu-P-3 and N-acetyl-2-aminofluorene (AAF) residues are equally efficient to induce the B-Z transition of poly(dG-dC).poly(dG-dC) and of poly(dA-dC).poly(dG-dT). Modifications of poly(dG).poly(dC) and calf thymus DNA indicate strong interactions between A-Glu-P-3 and the bases.

Animals↗