AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (May 10, 2005). doi:10.1152/ajpendo.00125.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/4/E695    most recent
00125.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elbatarny, H. S
Right arrow Articles by Maurice, D. H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elbatarny, H. S
Right arrow Articles by Maurice, D. H
Submitted on March 18, 2005
Accepted on May 5, 2005

Leptin-Mediated Activation of Human Platelets: Involvement of a Leptin Receptor and Phosphodiesterase 3A Containing Cellular Signaling Complex

Hisham S Elbatarny1 and Donald H Maurice1*

1 Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada

* To whom correspondence should be addressed. E-mail: mauriced{at}post.queensu.ca.

An elevated circulating level of the adipocyte-derived satiety hormone leptin is an independent risk factor for cardiovascular disease. Since thrombus formation is a major cause of acute coronary events and leptin was shown previously to facilitate ADP-induced platelet aggregation, we chose to define the signaling events involved in leptin-mediated platelet activation. Using pharmacological, biochemical and cell biological approaches we show that leptin-induced platelet activation required activation of a signaling cascade that included the long-form of the leptin receptor, three kinases (Janus kinase 2 (Jak2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB/Akt)), the insulin receptor substrate-1 (IRS-1) and the major human platelet cAMP phosphodiesterase, phosphodiesterase 3A (PDE3A). Moreover, we identify a role for an intraplatelet LEPR/Jak2/IRS-1/PI3K/PKB/PDE3A molecular complex that allows for the selective leptin-mediated activation of platelets. Our data demonstrate that leptin promotes platelet activation, provides a mechanistic basis for the prothrombotic effect of this hormone and identifies a potentially novel therapeutic avenue to limit obesity-associated cardiovascular disease.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. F. Bodary
Links Between Adipose Tissue and Thrombosis in the Mouse
Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2284 - 2291.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. Zhang and R. W. Colman
Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A
Blood, September 1, 2007; 110(5): 1475 - 1482.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Othman, A. Labelle, I. Mazzetti, H. S. Elbatarny, and D. Lillicrap
Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance
Blood, April 1, 2007; 109(7): 2832 - 2839.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.