کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5737694 | 1614726 | 2017 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of thrombin-PAR1-PKCθ/δ axis in brain pericytes in thrombin-induced MMP-9 production and blood-brain barrier dysfunction in vitro
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کلمات کلیدی
Rat brain endothelial cellPKCBMECphorbol 12-myristate 13-acetatePericyteERKMMP-9In vitro BBB modelRBECDMEMJnkHEPESFBS4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidc-Jun N-terminal kinase - C-Jun N-terminal kinasePMA - LDC هاMAPK - MAPKEDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدAlzheimer’s disease - بیماری آلزایمرParkinson’s disease - بیماری پارکینسونThrombin - ترومبین یا فاکتور II Par - توسطintracerebral hemorrhage - خونریزی داخل مغزیBlood–brain barrier - سد خونی مغزیBBB - سد خونی مغزیfetal bovine serum - سرم جنین گاوbrain microvascular endothelial cell - سلول اندوتلیال میکرو مغناطیسی مغز مغزCell signaling - سیگنالینگ سلولیactivating peptide - فعال کردن پپتیدSodium fluorescein - فلورسین سدیمMatrix metalloproteinase-9 - ماتریکس متالوپروتئیناز -9Dulbecco’s modified eagle’s medium - محیط عقاب اصلاح شده DulbeccoICH - منPermeability - نفوذپذیریProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیprotease-activated receptor - گیرنده پروتئاز فعال
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Thrombin, an essential component in the coagulation cascade, participates in the pathogenesis of brain diseases, such as ischemic stroke, intracerebral hemorrhage, Alzheimer's disease and Parkinson's disease through blood-brain barrier (BBB) dysfunction. It is thought that the thrombin-matrix metalloproteinase (MMP)-9 axis is an important process in the pathogenesis of neurovascular disease, such as BBB dysfunction. We recently reported that brain pericytes are the most MMP-9-releasing cells in response to thrombin stimulation among the BBB-constituting cells. This thrombin-induced MMP-9 release is partially due to protease-activated receptor (PAR1), one of the specific thrombin receptors. Then, we evaluated the intracellular signaling pathways involved in MMP-9 release and the contribution of thrombin-reactive brain pericytes to BBB dysfunction. PKC activator evoked MMP-9 release from brain pericytes. The thrombin-induced MMP-9 release was inhibited by U0126, LY294002, Go6976, and Go6983. However, Go6976 decreased phosphorylation levels of PKCθ and Akt, and Go6983 decreased phosphorylation levels of PKCδ and extracellular signal-regulated kinase (ERK). Additionally, treatment of pericytes with thrombin or PAR1-activating peptide stimulated PKCδ/θ signaling. These substances impaired brain endothelial barrier function in the presence of brain pericytes. Brain pericytes function through two independent downstream signaling pathways via PAR1 activation to release MMP-9 in response to thrombin - the PKCθ-Akt pathway and the PKCδ-ERK1/2 pathway. These pathways participate in PAR1-mediated MMP-9 release from pericytes, which leads to BBB dysfunction. Brain pericytes and their specific signaling pathways could provide novel therapeutic targets for thrombin-induced neurovascular diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 350, 14 May 2017, Pages 146-157
Journal: Neuroscience - Volume 350, 14 May 2017, Pages 146-157
نویسندگان
Takashi Machida, Shinya Dohgu, Fuyuko Takata, Junichi Matsumoto, Ikuya Kimura, Mariko Koga, Keiko Nakamoto, Atsushi Yamauchi, Yasufumi Kataoka,