4(1)). On the other hand, B-cell lymphoma protein-3 (Bcl-3), which is involved in clot retraction, is translated upon thrombin activation

and under mammalian target of rapamycin (mTOR) regulation, as shown in Fig. 4(2). Thrombin activation also increases synthesis of continuously translated proteins, such as plasminogen activator inhibitor (PAI-1). Finally, protein synthesis can also occur via a functional spliceosome, which has been found in platelets [4]. Indeed, pre-mRNAs exist in platelets and are spliced upon platelet activation (Fig. 4(3)). Tissue factors and interleukin 1 β are examples of such regulation. These different regulation mechanisms are facilitated by a strong interaction of mRNAs and protein synthesis machinery with the cytoskeleton, and the presence of translation www.selleckchem.com/products/BIRB-796-(Doramapimod).html factors such as protein eukaryotic initiation HDAC inhibitor factor, which is constitutively expressed. Platelet activation triggers a drastic cytoskeleton remodeling, which changes the localization of the different partners of protein synthesis. Platelet transcriptome was investigated in the context of the variability of platelet reactivity. RNA expression was assessed in 288 healthy individuals using microarray [57]. The expression level of VAMP8/endobrevin was positively associated with high platelet reactivity, as assessed with light transmission aggregometry. In addition, a SNP

(rs1010) and a microRNA (miRNA-96) were shown to be key players in VAMP8 modulation. Since VAMP8 is a

v-SNARE involved in the targeting and fusion of secretory granules to the plasma membrane, this study linked platelet reactivity variability to granule release. Recent data suggest that microRNA (miRNA) play an important role in mRNA regulation in platelets. These small nucleotides (around 22 base pairs) can induce mRNA degradation and either delay or promote translation [58]. Several mRNAs and their modulating miRNAs were recently associated with platelet reactivity in healthy subjects [59]. Among the 284 miRNAs expressed by platelets, Megestrol Acetate 74 were differentially expressed in different platelet reactivity categories. These data were combined with quantitative transcriptomic results on the same cohort, to obtain a list of paired miRNAs-mRNAs with a binding site at the 3′untranslated region (UTR) of mRNA. Among them, 3 pairs were of particular interest and could be validated at the level of protein expression. Although mRNAs and miRNAs play a role in the modulation of platelet function by transcriptomics, their exact role at the proteomic level, as well as their functional impact, remain unclear. Platelets have been extensively analyzed using proteomics [42] and [60]. Indeed, since platelets are anucleated and contain a limited amount of mRNA, their proteome is interesting for the study of their physiology. Recently, the platelet proteome was dramatically extended to reach almost 4000 proteins and 2500 phosphorylation sites [40].