کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6020401 | 1580397 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy
ترجمه فارسی عنوان
مهار کردن آدنوزین کیناز موجب کاهش التهاب و عصبی شدن عصب در نوروپاتی اپتیکی شدید
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کلمات کلیدی
LPSAKIMAPKinaseROS - ROSadenosine kinase - آدنوزین کینازinflammation - التهاب( توروم) Adenosine kinase inhibitor - بازدارنده آدنوزین کینازELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاTON - تنtumor necrosis factor-α - تومور نکروز عامل αTNF-α - فاکتور نکروز توموری آلفاLipopolysaccharides - لیپوپلی ساکارید هاMicroglia - میکروگلیاهاTraumatic optic neuropathy - نوروپاتی اپتیکی تروماتیکmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenMAP kinase - کیناز MAPextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیReactive oxygen species - گونههای فعال اکسیژنAdenosine receptor - گیرنده آدنوزین
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
چکیده انگلیسی
Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local productions of reactive oxygen species and inflammatory mediators from activated microglial cells have been hypothesized to underlie apoptotic processes. We previously demonstrated that the anti-inflammatory effect of adenosine, through A2A receptor activation had profound protective influence against retinal injury in traumatic optic neuropathy. This protective effect is limited due to rapid cellular re-uptake of adenosine by equilibrative nucleotside transporter-1 (ENT1) or break down by adenosine kinase (AK), the key enzyme in adenosine clearance pathway. Further, the use of adenosine receptors agonists are limited by systemic side effects. Therefore, we seek to investigate the potential role of amplifying the endogenous ambient level of adenosine by pharmacological inhibition of AK. We tested our hypothesis by comparing TON-induced retinal injury in mice with and without ABT-702 treatment, a selective AK inhibitor (AKI). The retinal-protective effect of ABT-702 was demonstrated by significant reduction of Iba-1, ENT1, TNF-α, IL-6, and iNOS/nNOS protein or mRNA expression in TON as revealed by western blot and real time PCR. TON-induced superoxide anion generation and nitrotyrosine expression were reduced in ABT-702 treated mice retinal sections as determined by immunoflourescence. In addition, ABT-702 attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells. The results of the present investigation suggested that ABT-702 had a protective role against marked TON-induced retinal inflammation and damage by augmenting the endogenous therapeutic effects of site- and event-specific accumulation of extracellular adenosine.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Neuroimmunology - Volume 277, Issues 1â2, 15 December 2014, Pages 96-104
Journal: Journal of Neuroimmunology - Volume 277, Issues 1â2, 15 December 2014, Pages 96-104
نویسندگان
Saif Ahmad, Nehal M. Elsherbiny, Kanchan Bhatia, Ahmed M. Elsherbini, Sadanand Fulzele, Gregory I. Liou,