کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738877 | 1046840 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
α-Tocopherol decreases tumor necrosis factor-α mRNA and protein from activated human monocytes by inhibition of 5-lipoxygenase
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کلمات کلیدی
TNFRRR-α-tocopherolCOXCycloxygenase5-LOLTB4PKC5-Lipoxygenase - 5-لیپوکسیژنازROS - ROSα-Tocopherol - α-توکوفرولβ-tocopherol - β-توکوفرولFree radicals - رادیکال آزادSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازCytokine - سیتوکینtumor necrosis factor - فاکتور نکروز تومورLeukotriene B4 - لوکوترین B4lipoxygenase - لیپواکسیژنازBIM - مدلسازی اطلاعات ساختمانMonocytes - مونوسیتهاProtein kinase C - پروتئین کیناز سیReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cardiovascular disease is the leading cause of morbidity in Westernized populations. Low levels of α-tocopherol (AT) are associated with increased incidence of atherosclerosis and increased intakes appear to be protective. AT supplementation decreases interleukin 1 and 6 release from human monocytes. Thus, the aim of this study was to examine the effect of AT on an important proinflammatory cytokine, tumor necrosis factor-α (TNF) release from human monocytes. AT supplementation (1200 IU/day for 3 months) significantly decreased TNF release from activated human monocytes. Mechanisms that were examined included its effect as a general antioxidant, its inhibitory effect on protein kinase C (PKC), and the cycloxygenase-lipoxygenase pathway. While AT decreased TNF release from activated monocytes, other antioxidants had no effect on TNF release. Specific PKC inhibitors had no effect on TNF release from activated monocytes. The inhibition of TNF release by AT in activated monocytes was reversed by leukotriene B4 (LTB4), a major product of the 5-lipoxygenase (5-LO) pathway. Similar observations were seen with inhibitors of 5-lipoxygenase. Indomethacin, a COX inhibitor, in the presence and absence of AT failed to affect TNF activity. These findings suggest that AT decreases TNF release from activated human monocytes via inhibition of 5-lipoxygenase. Also, AT as well as a 5-LO inhibitor significantly decreased TNF mRNA. Furthermore, AT and the 5-LO inhibitor decreased NFκb-binding activity. Thus, in activated human monocytes, AT appears to inhibit TNF mRNA and protein by inhibition of 5-LO.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 38, Issue 9, 1 May 2005, Pages 1212-1220
Journal: Free Radical Biology and Medicine - Volume 38, Issue 9, 1 May 2005, Pages 1212-1220
نویسندگان
Sridevi Devaraj, Ishwarlal Jialal,