کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8260475 | 1534663 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells
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کلمات کلیدی
MCP-1VCAM-1HSP27Retinal endothelial cellAc-DEVD-AFCIDOIFN-γCM-H2DCFDAIL-1βcox2HSF-1NOSICAM-1HRECDETA NONOate(Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolatel-NAME - L-NAMENω-nitro-l-arginine methyl ester hydrochloride - N-Nitro-L-Arginine Methyl Ester HydrochlorideROS - ROSONOO - اونوinterferon-γ - اینترفرون-γInterleukin-1β - اینترلوکین-1βindoleamine 2,3-dioxygenase - ایندولامین 2،3-دیوکسژیگنازtumor necrosis factor-α - تومور نکروز عامل αApoptosis - خزان یاختهایTempol - سریعHuman retinal endothelial cells - سلولهای اندوتلیال شبکیه انسانCytokine - سیتوکینCyclooxygenase-2 - سیکلوکوکسیژناز2Heat shock factor-1 - فاکتور شوک حرارت 1TNF-α - فاکتور نکروز توموری آلفاcytokine mixture - مخلوط سیتوکینintracellular adhesion molecule-1 - مولکول چسبندگی داخل سلولی -1vascular cell adhesion molecule-1 - مولکول چسبندگی سلولی عروقی-1Nitric oxide - نیتریک اکسیدnitric oxide synthase - نیتریک اکسید سنتازMonocyte chemotactic protein-1 - پروتئین chemotactic monocyte-1Peroxynitrite - پروکسی نیتریتhigh glucose - گلوکز بالا یا قند بالاReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells](/preview/png/8260475.png)
چکیده انگلیسی
The formation of acellular capillaries in the retina, a hallmark feature of diabetic retinopathy, is caused by apoptosis of endothelial cells and pericytes. The biochemical mechanism of such apoptosis remains unclear. Small heat shock proteins play an important role in the regulation of apoptosis. In the diabetic retina, pro-inflammatory cytokines are upregulated. In this study, we investigated the effects of pro-inflammatory cytokines on small heat shock protein 27 (Hsp27) in human retinal endothelial cells (HREC). In HREC cultured in the presence of cytokine mixtures (CM), a significant downregulation of Hsp27 at the protein and mRNA level occurred, with no effect on HSF-1, the transcription factor for Hsp27. The presence of high glucose (25Â mM) amplified the effects of cytokines on Hsp27. CM activated indoleamine 2,3-dioxygenase (IDO) and enhanced the production of kynurenine and ROS. An inhibitor of IDO, 1-methyl tryptophan (MT), inhibited the effects of CM on Hsp27. CM also upregulated NOS2 and, consequently, nitric oxide (NO). A NOS inhibitor, L-NAME, and a ROS scavenger blocked the CM-mediated Hsp27 downregulation. While a NO donor in the culture medium did not decrease the Hsp27 content, a peroxynitrite donor and exogenous peroxynitrite did. The cytokines and high glucose-induced apoptosis of HREC were inhibited by MT and L-NAME. Downregulation of Hsp27 by a siRNA treatment promoted apoptosis in HREC. Together, these data suggest that pro-inflammatory cytokines induce the formation of ROS and NO, which, through the formation of peroxynitrite, reduce the Hsp27 content and bring about apoptosis of retinal capillary endothelial cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1842, Issue 2, February 2014, Pages 164-174
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1842, Issue 2, February 2014, Pages 164-174
نویسندگان
Rooban B. Nahomi, Allison Palmer, Katelyn M. Green, Patrice E. Fort, Ram H. Nagaraj,