دورية أكاديمية
أعرض في EDS

Platelet activity is negatively modulated by tumor necrosis factor alpha through reductions of cytosolic calcium levels and integrin alphaIIbbeta3 phosphorylation.

التفاصيل البيبلوغرافية
العنوان: Platelet activity is negatively modulated by tumor necrosis factor alpha through reductions of cytosolic calcium levels and integrin alphaIIbbeta3 phosphorylation.
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
الوصف
تدمد:1879-2472
DOI:10.1016/j.thromres.2018.10.008