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Cathepsin G and thrombin: evidence for two different platelet receptors.

ABSTRACT: Neutrophil cathepsin G and thrombin, the only platelet agonists that are proteases, exhibit a mandatory requirement for catalytic activity to induce platelet aggregation and signal transduction. The thrombin receptor is a G-protein-coupled receptor which undergoes proteolysis to generate a tethered ligand that causes self-activation. Since cathepsin G strongly resembles thrombin in its ability to activate platelets, we have attempted to determine whether cathepsin G and thrombin function through the same or different receptors. Evidence that thrombin and cathepsin G act at different receptors was as follows: (a) an antibody directed against the thrombin receptor blocked thrombin-induced but not cathepsin G-induced platelet responses; (b) human fibroblasts responded to thrombin and to a synthetic thrombin receptor peptide (comprising residues 42-55 of the thrombin receptor) by exhibiting an elevation in cytosolic Ca2+ concentration but did not respond to cathepsin G; and (c) platelets pretreated with neutrophil elastase failed to respond to thrombin but responded when rechallenged by cathepsin G. Thrombin and cathepsin G exhibit heterologous desensitization that is potentiated by okadaic acid and is attenuated by staurosporine, indicating that phosphorylation of serine/threonine residues is important for desensitization and that protein kinase C may be involved. Since catalytic activity of cathepsin G is required for platelet stimulation, it is probable that platelet activation by cathepsin G requires receptor proteolysis and that a tethered ligand mechanism is involved, suggesting that platelets may possess a family of protease receptors.

SUBMITTER: Selak MA

PROVIDER: S-EPMC1137824 | biostudies-other | 1994 Jan

REPOSITORIES: biostudies-other

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Fibrinogen-elongated gamma chain inhibits thrombin-induced platelet response, hindering the interaction with different receptors.

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Differential involvement of thrombin receptors in Ca2+ release from two different intracellular stores in human platelets.

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| S-EPMC1216922 | biostudies-other

Thrombin-reduced miR-27b attenuates platelet angiogenic activities via enhancing platelet de novo synthesis of anti-angiogenic thrombospondin-1

Project description:To identify if platelet activation would result in altered platelet miRNA profile, not only in total RNA sample, also in AGO2-immunoprecipitation(AGO2-IP) products. To determinate if altered platelet miRNAs could regulate de novo protein synthesis of angiogenic factors in activated platelets, and even more importantly, if miRNA-regulated platelet angiogenic factor synthesis could result in changes of platelet angiogenic activities.

2017-03-14 | GSE96533 | GEO

The canine activated platelet secretome (CAPS): A translational model of thrombin-evoked platelet activation response.

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| S-EPMC7845059 | biostudies-literature

Proteomic profiling of the thrombin-activated canine platelet secretome (CAPS).

Project description:Domestic dogs share the same environment as humans, and they represent a valuable animal model to study naturally-occurring human disease. Platelet proteomics holds promise for the discovery of biomarkers that capture the contribution of platelets to the pathophysiology of many disease states, however, canine platelet proteomic studies are lacking. Our study objectives were to establish a protocol for proteomic identification and quantification of the thrombin-activated canine platelet secretome (CAPS), and to compare the CAPS proteins to human and murine platelet proteomic data. Washed platelets were isolated from healthy dogs, and stimulated with saline (control) or gamma-thrombin (releasate). Proteins were separated by SDS-page, trypsin-digested and analyzed by liquid chromatography and tandem mass spectrometry (MS). CAPS proteins were defined as those with a MS1-abundance ratio of two or more for releasate vs. unstimulated saline control. A total of 1,918 proteins were identified, with 908 proteins common to all dogs and 693 characterized as CAPS proteins. CAPS proteins were similar to human and murine platelet secretomes and were highly represented in hemostatic pathways. Differences unique to CAPS included replacement of platelet factor 4 with other cleavage products of platelet basic protein (e.g. interleukin-8), novel proteins (e.g. C-C motif chemokine 14), and proteins in relatively high (e.g. protease nexin-1) or low (e.g. von Willebrand factor) abundance. This study establishes the first in-depth platelet releasate proteome from healthy dogs with a reference database of 693 CAPS proteins. Similarities between CAPS and the human secretome confirm the utility of dogs as translational models of human disease, but we also identify differences unique to canine platelets. Our findings provide a resource for further investigations into disease-related CAPS profiles, and for comparative pathway analyses of platelet activation among species.

| S-EPMC6853320 | biostudies-literature

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