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Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity

Title
Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity
Authors
Kim, KeunyoungShin, Eun-KyungChung, Jin-HoLim, Kyung-Min
Ewha Authors
임경민김근영
SCOPUS Author ID
임경민scopus
Issue Date
2020
Journal Title
TOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN
0041-008XJCR Link

1096-0333JCR Link
Citation
TOXICOLOGY AND APPLIED PHARMACOLOGY vol. 391
Keywords
ArsenicPlateletThrombosisPlatelet shape changeFocal adhesion kinaseActin dynamics
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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.
DOI
10.1016/j.taap.2020.114912
Appears in Collections:
약학대학 > 약학과 > Journal papers
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