Role of p38 Mitogen-Activated Protein Kinase in Thrombus Formation

Sakurai, Kazutoshi; Matsuo, Yuji; Sudo, Tatsuhiko; Takuwa, Yoh; Kimura, Sadao; Kasuya, Yoshitoshi

doi:10.1081/rrs-200040324

Cited by 32 publications

(28 citation statements)

References 31 publications

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“…Thus, platelets possibly act to facilitate all of the intermediate steps of transvascular metastasis, including tumor cell retention and arrest, subendothelial interaction, and extravasation from the microvasculature. We recently demonstrated that the binding activity of activated platelets from p38␣ ϩ/Ϫ mice to fibrinogen, possibly mediated through integrin ␣IIb␤3, is suppressed compared with the case of platelets from WT mice (9). This clearly indicates that the function of platelets is attenuated in p38␣ ϩ/Ϫ mice compared with WT mice.…”

Section: Reduction Of Tumor Cell-platelet Interaction In P38␣mentioning

confidence: 85%

“…Tumors were measured along the plane of the body cavity using a hand caliper, and tumor volume was calculated as (length ϫ width) 2 /2. In Vitro Binding of Platelets to Tumor Cells-Platelets were prepared from WT and p38␣ ϩ/Ϫ mice by the method previously described (9). Then platelets were fluorescently labeled with calcein by incubation with 1 M calcein-acetoxymethyl ester (Molecular Probes) for 30 min at 37°C and washed twice with Hepes-Tyrode's buffer (10 mM Hepes, 137 mM NaCl, 2.68 mM KCl, 0.42 mM NaH 2 PO 4 , 1.7 mM MgCl 2 , 11.9 mM NaHCO 3 , 5 mM glucose, pH 7.2).…”

Section: Methodsmentioning

confidence: 99%

“…Among them, p38␣ and -␤ are expressed relatively ubiquitously, as shown by Northern blot analysis of adult tissues (4). Although targeted disruption of the p38␣ gene results in homozygous embryonic lethality because of defects in erythropoiesis and placental organogenesis (5,6), the p38␣ ϩ/Ϫ mouse is a useful tool for analyzing the in vivo role of p38 in disease models (7)(8)(9).…”

Section: Mice Platelets Of P38␣mentioning

confidence: 99%

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Involvement of p38α Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells

Matsuo

Amano

Furuya

et al. 2006

Journal of Biological Chemistry

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To study the role of p38 mitogen-activated protein kinase (p38) activity during the process of metastasis, p38␣؉/؊ mice were subjected to an in vivo metastasis assay. The number of lung colonies of tumor cells intravenously injected in p38␣ ؉/؊ mice was markedly decreased compared with that in wild-type (WT) mice. On the other hand, the time-dependent increase in tumor volume after subcutaneous tumor cells transplantation was comparable between WT and p38␣ mice. Platelets of p38␣؉/؊ mice were poorly bound to tumor cells in vitro and in vivo compared with those of WT mice. Eand P-selectin mRNAs were markedly induced in the lung after intravenous injection of tumor cells. However, the induction of these selectin mRNAs in p38␣ ؉/؊ mice was weaker than that in WT mice. Furthermore, the resting expression levels of E-selectin in lung endothelial cells and P-selectin in platelets of p38␣

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Section: Reduction Of Tumor Cell-platelet Interaction In P38␣mentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Mice Platelets Of P38␣mentioning

confidence: 99%

See 1 more Smart Citation

Involvement of p38α Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells

Matsuo

Amano

Furuya

et al. 2006

Journal of Biological Chemistry

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“…In platelet biology, MAP kinases have not been studied in detail, although it has been demonstrated that the P2Y 1 ADP receptor activates p38 MAP kinase, and p38-deficient mice have prolonged thrombotic occlusion time in a ferric chloride (FeCl 3 )-induced thrombosis model. 21,22 We, thus, hypothesized that CD36-mediated platelet activation might involve specific members of the src and MAP kinase families.…”

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confidence: 99%

A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein

Chen

Febbraio

et al. 2008

Circulation Research

169

181

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Abstract-Platelet hyperactivity associated with hyperlipidemia may contribute to development of a prothrombotic state.We previously showed that oxidized low-density lipoprotein (oxLDL) formed in the setting of hyperlipidemia and atherosclerosis activated platelets in a CD36-dependent manner. We now show that mitogen-activated protein kinase c-Jun N-terminal kinase (JNK)2 and its upstream activator MKK4 were phosphorylated in platelets exposed to oxLDL. Using apoE Ϫ/Ϫ mice as a model of hyperlipidemia, we showed that JNK was constitutively phosphorylated in platelets in a CD36-dependent manner. Inhibition of src kinase activity reduced JNK phosphorylation by oxLDL. Immunoprecipitations revealed that active phosphorylated forms of src kinases Fyn and Lyn were recruited to CD36 in platelets exposed to oxLDL. Pharmacological inhibition of the mitogen-activated protein kinase JNK or src family kinases abolished platelet activation by oxLDL in vitro. Using a murine carotid artery thrombosis model we demonstrated CD36-dependent phosphorylation of platelet JNK within thrombi. Furthermore, pharmacological inhibition of JNK prolonged thrombosis times in wild-type but not cd36-null mice in vivo. These findings suggest that a specific CD36-dependent signaling pathway is required for platelet activation by oxLDL and may provide insights related to development of novel antiplatelet therapies more relevant to atherothrombosis than to normal hemostasis. (Circ Res. 2008;102:1512-1519.)Key Words: CD36 Ⅲ JNK Ⅲ thrombosis Ⅲ hyperlipidemia C D36 is an integral membrane protein expressed on monocytes/macrophages, 1 platelets, 2 microvascular endothelium, 1 fat, and muscle. 3,4 Although initially identified as a receptor for thrombospondin-1 and malaria-infected erythrocytes, 5,6 it is now known to be a class B scavenger receptor that recognizes several unrelated ligands, including thrombospondin-1 and -2, 7,8 oxidized phospholipids expressed on oxidized low-density lipoprotein (oxLDL) and apoptotic cell surfaces, 9,10 long chain fatty acids, 11 amyloidogenic peptides, 12 and specific components of microbial cell walls or cell surfaces. 13 CD36 is involved in a variety of biological processes including lipid metabolism, inflammation, atherosclerosis, and angiogenesis, depending on the nature of the ligand to which it is exposed and the cell or tissue type on which it is expressed. 14 Although CD36 was first isolated and structurally characterized from platelets, 2 its functional role on platelets remains incompletely characterized. OKM5, a monoclonal antibody directed against CD36, was observed many years ago to induce platelet activation and aggregation. 15 Although the effect was dependent on expression of Fc receptors, it could be blocked by F(abЈ) 2 fragments of the antibody, suggesting that the CD36 epitope was required and that CD36 may transduce platelet activating signals. Many other CD36 monoclonal antibodies have also been shown to have stimulatory effects on platelets. 16 Our group in collaboration with others recently sho...

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“…Furthermore, a holistic approach to managing fertility will be necessary, as stem cell transplantation has been reported to affect multiple factors that alter it, including chronic GVHD 7 and longterm psychological health. 8,9 This study demonstrates that the ferocity of acute GVHD affects feracitas and thus raises important…”

mentioning

confidence: 99%

Stressed platelets ASK1 for a MAPK

Flaumenhaft

2017

Blood

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Role of p38 Mitogen-Activated Protein Kinase in Thrombus Formation

Cited by 32 publications

References 31 publications

Involvement of p38α Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells

Involvement of p38α Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells

A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein

Stressed platelets ASK1 for a MAPK

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