دورية أكاديمية
Platelet activity is negatively modulated by tumor necrosis factor alpha through reductions of cytosolic calcium levels and integrin alphaIIbbeta3 phosphorylation.
العنوان: | Platelet activity is negatively modulated by tumor necrosis factor alpha through reductions of cytosolic calcium levels and integrin alphaIIbbeta3 phosphorylation. |
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المؤلفون: | Bonfitto PHL; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Naime ACA; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Lopes-Pires ME; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Goulart G; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Mendes-Silverio CB; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Bueno PI; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Castilho RF; Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Antunes E; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Marcondes S; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: sisimp@fcm.unicamp.br. |
المصدر: | Thrombosis research [Thromb Res] 2018 Dec; Vol. 172, pp. 44-50. Date of Electronic Publication: 2018 Oct 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Pergamon Press Country of Publication: United States NLM ID: 0326377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2472 (Electronic) Linking ISSN: 00493848 NLM ISO Abbreviation: Thromb Res Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Elmsford, N. Y., Pergamon Press. |
مواضيع طبية MeSH: | Platelet Aggregation*, Blood Platelets/*metabolism , Calcium/*metabolism , Integrin beta3/*metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/*metabolism , Platelet Membrane Glycoprotein IIb/*metabolism , Tumor Necrosis Factor-alpha/*metabolism, Animals ; Blood Platelets/cytology ; Cyclic GMP/metabolism ; Cytosol/metabolism ; Male ; Phosphorylation ; Rats, Wistar |
مستخلص: | Introduction: Tumor necrosis factor-alpha (TNF-α) exerts a critical role in inflammatory events through two distinct receptors, TNFR1 and TNFR2. Platelets have been recognized as important inflammatory cells, but little is known about the effects of TNF-α on the platelet activity. Objectives: In the present study we have studied the role of TNF-α on ADP-induced platelet aggregation and its downstream signaling (c-Src and fibrinogen receptor phosphorylation, cytosolic Ca 2+ mobilization, cAMP and cGMP levels and cell viability). Methods and Results: Washed rat platelets were incubated with TNF-α (1-3000 pg/ml) for different time-periods (5-60 min) before the addition of ADP (5 μM) to induce platelet aggregation. TNF-α concentration- and time-dependently inhibits ADP-induced aggregation, which was significantly prevented by incubation with the non-selective TNF-α receptor antagonist R7050. TNF-α (300 pg/ml, 30 min) decreases thrombin-induced elevation of cytosolic Ca ++ levels by 2.2- fold compared to untreated platelets. TNF-α decreases the cAMP levels, while significantly increases the intracellular cyclic cGMP levels. However, the pre-incubation of platelets with the guanylyl cyclase inhibitor ODQ, despite decreasing the cGMP levels, does not modify the inhibitory effect of TNF-α on ADP-induced platelet aggregation. Additionally, western blotting analysis showed that TNF-α significantly reduced (Tyr 416)-c-Src and (Tyr773)-β3 subunit of αIIbβ3 integrin phosphorylation. TNF-α does not affect the platelet viability in any condition tested. Conclusion: Therefore, our results show that TNF-α negatively modulates ADP-induced aggregation via TNFR1/TNFR2 receptors by reducing cytosolic Ca ++ levels and by inhibiting c-Src and fibrinogen receptor activation, which take place through cAMP- and cGMP-independent mechanisms. (Copyright © 2018 Elsevier Ltd. All rights reserved.) |
فهرسة مساهمة: | Keywords: C-Src; Calcium mobilization; Cyclic GMP; Integrin alphaIIbbeta3; Platelet aggregation |
المشرفين على المادة: | 0 (Integrin beta3) 0 (Platelet Glycoprotein GPIIb-IIIa Complex) 0 (Platelet Membrane Glycoprotein IIb) 0 (Tumor Necrosis Factor-alpha) H2D2X058MU (Cyclic GMP) SY7Q814VUP (Calcium) |
تواريخ الأحداث: | Date Created: 20181026 Date Completed: 20190114 Latest Revision: 20190114 |
رمز التحديث: | 20221213 |
DOI: | 10.1016/j.thromres.2018.10.008 |
PMID: | 30359790 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1879-2472 |
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DOI: | 10.1016/j.thromres.2018.10.008 |