2012
DOI: 10.1111/j.1538-7836.2012.04857.x
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Protein kinase Cε and protein kinase Cθ double‐deficient mice have a bleeding diathesis

Abstract: SummaryBackground: In comparison to the classical isoforms of protein kinase C (PKC), the novel isoforms are thought to play minor or inhibitory roles in the regulation of platelet activation and thrombosis.Objectives:To measure the levels of PKCθ and PKCε and to investigate the phenotype of mice deficient in both novel PKC isoforms.Methods:Tail bleeding and platelet activation assays were monitored in mice and platelets from mice deficient in both PKCθ and PKCε.Results:PKCε plays a minor role in supporting ag… Show more

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Cited by 9 publications
(5 citation statements)
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“…33 Thrombus formation in laminar flow was carried out as described in glass capillary tubes coated with collagen, and perfusion for 4 minutes at 1000 s 21 of heparinized whole blood taken from the inferior vena cava. 34 Platelet thrombi volume was assessed after lysis with 50 mL Nonidet P-40 lysis buffer (300 mM NaCl 2 , 20 mM tris(hydroxymethyl)aminomethane-HCl, 2 mM EGTA, 2 mM EDTA, 2% Nonidet P-40, 2 mM Na 3 VO 4 , 1 mM 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, 1 mg/mL leupeptin, 10 mg/mL aprotinin, 1 mg/mL pepstatin), and protein quantification was carried out by western blot using a tubulin antibody.…”
Section: Tail-bleeding Assay and Thrombus Formation Under Flowmentioning
confidence: 99%
“…33 Thrombus formation in laminar flow was carried out as described in glass capillary tubes coated with collagen, and perfusion for 4 minutes at 1000 s 21 of heparinized whole blood taken from the inferior vena cava. 34 Platelet thrombi volume was assessed after lysis with 50 mL Nonidet P-40 lysis buffer (300 mM NaCl 2 , 20 mM tris(hydroxymethyl)aminomethane-HCl, 2 mM EGTA, 2 mM EDTA, 2% Nonidet P-40, 2 mM Na 3 VO 4 , 1 mM 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, 1 mg/mL leupeptin, 10 mg/mL aprotinin, 1 mg/mL pepstatin), and protein quantification was carried out by western blot using a tubulin antibody.…”
Section: Tail-bleeding Assay and Thrombus Formation Under Flowmentioning
confidence: 99%
“…Indeed, the bleeding time of injured PKCθ-deficient mice was longer than that of wild-type mice [37] and their ability to respond by thrombus formation after arterial injury was also impaired [38]. These results are somewhat controversial [29], although a recent study demonstrated an additive negative effect of PKCθ and PKCε deficiency on mouse bleeding [48].…”
Section: Pkcθ-mediated Regulation Of Platelet Activation and Aggregationmentioning
confidence: 91%
“…The protein kinase C (PKC) signaling pathway regulates the platelet response in thrombus formation, where the proteins PKCε and PKCδ play a crucial role in this process [ 73 , 74 , 75 ]. In the activation of GPVI with collagen, the protein PKCε promotes platelet spreading, secretion, and aggregation [ 76 ]. On the other hand, PKC-θ also helps to support adhesion and filopodial generation, but does not affect GPVI-stimulated aggregation or secretion.…”
Section: Platelet Signaling Pathways Related To Gpvi Activationmentioning
confidence: 99%
“…On the other hand, PKC-θ also helps to support adhesion and filopodial generation, but does not affect GPVI-stimulated aggregation or secretion. In contrast, the lack of both isoforms in a murine model showed a significant decrease in aggregation induced by collagen, with a considerable increase in a tail bleeding study [ 76 ]. Moreover, studies show that PKC-θ is activated by GPVI agonists; observing a knockout PKC-θ murine model (model of thrombosis induced with FeCl 3 ) led to a compromised hemostasis, prolonged bleeding time, an unstable formation of thrombi, and extended arterial occlusion [ 77 , 78 ].…”
Section: Platelet Signaling Pathways Related To Gpvi Activationmentioning
confidence: 99%