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Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity
- Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity
- Kim, Keunyoung; Shin, Eun-Kyung; Chung, Jin-Ho; Lim, Kyung-Min
- Ewha Authors
- 임경민; 김근영
- SCOPUS Author ID
- Issue Date
- Journal Title
- TOXICOLOGY AND APPLIED PHARMACOLOGY
- TOXICOLOGY AND APPLIED PHARMACOLOGY vol. 391
- Arsenic; Platelet; Thrombosis; Platelet shape change; Focal adhesion kinase; Actin dynamics
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- SCI; SCIE; SCOPUS
- Document Type
- Arsenic, an environmental contaminant in drinking water worldwide is well-established to increase cardiovascular diseases (CVDs) in humans. Of these, thrombotic events represent a major adverse effect associated with arsenic exposure, for which an abundance of epidemiological evidence exists. Platelet aggregation constitutes a pivotal step in thrombosis but arsenic alone doesn't induce aggregation and the mechanism underlying arsenic-induced thrombosis still remains unclear. Here we demonstrated that arsenic induces morphological changes of platelets, ie., contraction and pseudopod projection, the primal events of platelet activation, which can increase platelet reactivity. Arsenite induced prominent platelet shape changes in a dose-dependent manner in freshly isolated human platelets. Of note, arsenite suppressed focal adhesion kinase (FAK) activity, which in turn activated RhoA, leading to altered actin assembly through LIMK activation, and subsequent cofilin inactivation. Arsenic-induced platelet shape change appeared to increase the sensitivity to thrombin and ADP-induced aggregation. Supporting this, latrunculin A, an inhibitor of actin-dynamics abolished it. Taken together, we demonstrated that arsenic induces cytoskeletal changes and shape changes of platelets through FAK-mediated alteration of actin dynamics, which renders platelets reactive to activating stimuli, ultimately contributing to increased thrombosis.
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