[en] Background. Platelet activation requires sweeping morphological changes,
supported by contraction and remodelling of platelet actin cytoskeleton. In various
other cell types, AMP-activated protein kinase (AMPK) controls the phosphorylation
state of cytoskeletal targets.
Objective. We hypothesized that AMPK is activated during platelet aggregation and
contributes to the control of cytoskeletal targets.
Results. We found that AMPK-α1 was mainly activated by thrombin and not by other
platelet agonists in purified human platelets. Thrombin activated AMPK-α1 ex vivo
via a Ca2+/calmodulin-dependent kinase kinase β (CAMKKβ)-dependent pathway.
Pharmacological inhibition of CAMKKβ blocked thrombin-induced platelet
aggregation and counteracted thrombin-induced phosphorylation of several
cytoskeletal proteins, namely, regulatory myosin light chains (MLC), cofilin and
vasodilator-stimulated phosphoprotein (VASP), three key elements involved in actin
cytoskeleton contraction and polymerization. Platelets isolated from mice lacking
AMPK-α1 exhibited reduced aggregation in response to thrombin, associated with a
defect in MLC, cofilin and VASP phosphorylation and actin polymerization. More
importantly, we show for the first time that AMPK pathway was activated in platelets
of patients undergoing major cardiac surgery, in a heparin-sensitive manner.
Conclusion. AMPK-α1 is activated by thrombin in human platelets. It controls
phosphorylation of key cytoskeletal targets and actin cytoskeleton remodelling during
platelet aggregation.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Onselaer, Marie-Blanche; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
Oury, Cécile ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Hunter, Roger W; Nestlé Institute of Health Sciences SA, Campus EPFL, Lausanne, Suisse
Eeckhoudt, Stéphane; Université Catholique de Louvain - UCL > Department of Hematology
Barile, Nicolas; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
LECUT, Christelle ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Morel, Nicole; Université Catholique de Louvain - UCL > Institute of Neuroscience, Laboratory of Cell Physiology, Brussels
Jacquet, Luc-Marie; Université Catholique de Louvain - UCL > Cliniques Universitaires Saint-Luc, Cardiovascular Intensive Care
Bertrand, Luc; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
Sakamoto, Kei; Nestlé Institute of Health Sciences SA, Campus EPFL, Lausanne, Switzerland
Vanoverschelde, Jean-Louis; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
Beauloye, Christophe; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
Horman, Sandrine; Université Catholique de Louvain - UCL > Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Recherche Cardiovasculaire
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