TY - JOUR T1 - Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry JF - Biology Open JO - Biology Open SP - 916 LP - 923 DO - 10.1242/bio.20135314 VL - 2 IS - 9 AU - Gorudko, Irina V. AU - Sokolov, Alexey V. AU - Shamova, Ekaterina V. AU - Grudinina, Natalia A. AU - Drozd, Elizaveta S. AU - Shishlo, Ludmila M. AU - Grigorieva, Daria V. AU - Bushuk, Sergey B. AU - Bushuk, Boris A. AU - Chizhik, Sergey A. AU - Cherenkevich, Sergey N. AU - Vasilyev, Vadim B. AU - Panasenko, Oleg M. Y1 - 2013/09/15 UR - http://bio.biologists.org/content/2/9/916.abstract N2 - Myeloperoxidase (MPO) is a heme-containing enzyme released from activated leukocytes into the extracellular space during inflammation. Its main function is the production of hypohalous acids that are potent oxidants. MPO can also modulate cell signaling and inflammatory responses independently of its enzymatic activity. Because MPO is regarded as an important risk factor for cardiovascular diseases associated with increased platelet activity, we studied the effects of MPO on human platelet functional properties. Laser scanning confocal microscopy was used to reveal carbohydrate-independent MPO binding to human platelet membrane. Adding MPO to platelets did not activate their aggregation under basal conditions (without agonist). In contrast, MPO augmented agonist-induced platelet aggregation, which was not prevented by MPO enzymatic activity inhibitors. It was found that exposure of platelets to MPO leads to actin cytoskeleton reorganization and an increase in their elasticity. Furthermore, MPO evoked a rise in cytosolic Ca2+ through enhancement of store-operated Ca2+ entry (SOCE). Together, these findings indicate that MPO is not a direct agonist but rather a mediator that binds to human platelets, induces actin cytoskeleton reorganization and affects the mechanical stiffness of human platelets, resulting in potentiating SOCE and agonist-induced human platelet aggregation. Therefore, an increased activity of platelets in vascular disease can, at least partly, be provided by MPO elevated concentrations. ER -