کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478606 | 1551144 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
NADPH oxidase mediates TNF-α-evoked in vitro brain barrier dysfunction: roles of apoptosis and time
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کلمات کلیدی
HBMECsMMPNaFPBSFBSHASHBSSTEEREBADPITJs - TJSHuman astrocytes - آستروسیت های انسانیtight junctions - اتصالات محکمNADPH oxidase - اکسیداز NADPH tumour necrosis factor-alpha - تومور نکروز عامل آلفاDiphenyleneiodonium - دیفنیلن اندونیمBlood–brain barrier - سد خونی مغزیBBB - سد خونی مغزیfoetal bovine serum - سرم جنین گاوHuman brain microvascular endothelial cells - سلول های اندوتلیال میکرو عروقی مغز انسانTNF-α - فاکتور نکروز توموری آلفاSodium fluorescein - فلورسین سدیمmatrix metalloproteinase - ماتریکس متالوپروتئینازPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریHank's balanced salt solution - محلول نمک متعادل هانکtransendothelial electrical resistance - مقاومت الکتریکی transendothelialCytoskeleton - چارچوب یاخته، سیتواسکلتون، اسکلت سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The pro-inflammatory cytokine TNF-α severely perturbs the integrity of the blood-brain barrier (BBB). This study explored the specific roles of NADPH oxidase and associated downstream effectors by using human brain microvascular endothelial cells (HBMECs) and human astrocytes (HAs), the key components of BBB, alone or in co-cultures to mimic human BBB. Exposure to TNF-α (6 h) impaired BBB integrity as evidenced by marked decreases in transendothelial electrical resistance and concurrent increases in paracellular flux which appeared to subside with time (24 h). Increased barrier dysfunction concurred with increases in endothelial NADPH oxidase activity, O2â production, actin stress fibre formation, MMP-2/9 activities and concomitant decreases in antioxidant (CuZn-SOD and catalase) and tight junction (claudin-5 and occludin) protein expressions. Conversely, TNF-α did not affect astrocytic MMP activities and antioxidant enzyme expressions. Unlike BBB damage, rates of HBMEC and HA apoptosis increased by time. Suppression of NADPH oxidase by apocynin or diphenyleneiodonium prevented TNF-α-evoked morphological changes and apoptosis, attenuated endothelial MMP activity and helped retain usual tight junction protein expression and barrier function. In conclusion, HBMECs constitute the main source of oxidative stress and basement-membrane degrading endopeptidases in inflammatory conditions associated with excessive release of TNF-α where targeting NADPH oxidase may prove extremely beneficial in maintaining proper barrier activity through prevention of cytoskeletal and tight junction reorganisations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 61, July 2014, Pages 72-84
Journal: Molecular and Cellular Neuroscience - Volume 61, July 2014, Pages 72-84
نویسندگان
Zuraidah Abdullah, Ulvi Bayraktutan,