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Journal articles
A serotonin-induced N-glycan switch regulates platelet aggregation.
Abstract : Serotonin (5-HT) is a multifunctional signaling molecule that plays different roles in a concentration-dependent manner. We demonstrated that elevated levels of plasma 5-HT accelerate platelet aggregation resulting in a hypercoagulable state in which the platelet surface becomes occupied by several glycoproteins. Here we study the novel hypothesis that an elevated level of plasma 5-HT results in modification of the content of N-glycans on the platelet surface and this abnormality is associated with platelet aggregation. Mass spectrometry of total surface glycoproteins on platelets isolated from wild-type mice infused for 24 hours with saline or 5-HT revealed that the content of glycoproteins on platelets from 5-HT-infused mice switched from predominantly N-acetyl-neuraminic acid (Neu5Ac) to N-glycolyl-neuraminic acid (Neu5Gc). Cytidine monophosphate-N-acetylneuraminate hydroxylase (CMAH) synthesizes Neu5Gc from Neu5Ac. Up-regulation of Neu5Gc content on the platelet surface resulted from an increase in the catalytic function, not expression, of CMAH in platelets of 5-HT-infused mice. The highest level of Neu5Gc was observed in platelets of 5-HT-infused, 5-HT transporter-knock out mice, suggesting that the surface delineated 5-HT receptor on platelets may promote CMAH catalytic activity. These new findings link elevated levels of plasma 5-HT to altered platelet N-glycan content, a previously unrecognized abnormality that may favor platelet aggregation.
Cited literature [46 references]
https://www.hal.inserm.fr/inserm-00996761
Contributor : Luc Maroteaux <>
Submitted on : Wednesday, May 28, 2014 - 10:34:24 AM
Last modification on : Wednesday, November 25, 2020 - 12:08:06 PM
Long-term archiving on: : Thursday, August 28, 2014 - 10:46:02 AM
Contributor : Luc Maroteaux <>
Submitted on : Wednesday, May 28, 2014 - 10:34:24 AM
Last modification on : Wednesday, November 25, 2020 - 12:08:06 PM
Long-term archiving on: : Thursday, August 28, 2014 - 10:46:02 AM
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srep02795.pdf
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