Objectif Endothelial cells in the blood vessels wall respond to mechanical forces by a variety of biological events (NO synthesis, PGI2 secretion, tPA expression, endothelin mRNA modulation, mitosis, etc.). The signalling mechanism between physical stimulus and biological event is still completely unknown. Mechano-sensitive pathways in Ca2+ signalling in human endothelial cells will be studied by a combination of cyto- and molecular biological techniques with simultaneous patch-clamp and intracellular Ca2+ measurements. Mechanical stimulation activates a Cl- conductance in endothelial cells. A study will be made of whether this conductance is related to the mdr-1 gene product P-glycoprotein. Also a possible G-protein mediated activation of this channel will be investigated. Another mechanism to provide mechano-sensitivity to endothelial cells is a mechanically induced release of intracellular calcium which depletes intracellular stores for calcium. A study will be made of whether the mechanical activation of PLC or PLA2 is involved in this mechano-sensitive signalling pathway. A possible role of the cytoskeleton will be approached by modulating the mechano-response with compounds that interfere with the actin-cytoskeleton. Mechanical stimulation of endothelial cells induces also Ca2+ entry. A study will be made of whether this entry is related to the filling state of intracellular Ca2+ stores. Contribution of a directly gated Ca2+ entry will be studied especially in relation to the possibly channel forming, actin binding protein, annexin 2. For this reason, endothelial cells will be transfected with a annexin-p11 binding construct. This construction forms large p11-annexin II aggregates which may immobilise the functional active annexins, and modulate the mechano-responses on Ca2+ entry. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Thème(s) 42 - Physical Chemical Biology Appel à propositions Data not available Régime de financement Data not available Coordinateur Katholieke Universiteit Leuven Contribution de l’UE Aucune donnée Adresse Campus Gasthuisberg O/N - Herestraat 49 3000 Leuven Belgique Voir sur la carte Coût total Aucune donnée Participants (4) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Institut National de la Santé et de la Recherche Médicale France Contribution de l’UE Aucune donnée Adresse 34295 Montpellier Voir sur la carte Coût total Aucune donnée Institute of Physiology and Biophysics Ouzbékistan Contribution de l’UE Aucune donnée Adresse 700095 Tashkent Voir sur la carte Coût total Aucune donnée Institute of Theoretical and Experimental Biophysics Russie Contribution de l’UE Aucune donnée Adresse 142292 Pushchino, Moscow Voir sur la carte Coût total Aucune donnée Russian Academy of Sciences Russie Contribution de l’UE Aucune donnée Adresse 194064 St. Petersburg Voir sur la carte Coût total Aucune donnée
