کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10802914 | 1055733 | 2010 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
α9β1 integrin engagement inhibits neutrophil spontaneous apoptosis: Involvement of Bcl-2 family members
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کلمات کلیدی
ECMNF-κBPI3KJnkFAKERKVCAM-1Bcl-xLPMNc-Jun Kinase - C-Jun KinaseADAM - آدامIntegrin - اینتگرینa disintegrin and metalloprotease - تخریب و متالوپروتئازApoptosis - خزان یاختهایSignaling - سیگنالینگnuclear factor-κB - فاکتور هسته ای κBDisintegrin - فساد اداریphosphatidylinositol-3-kinase - فسفاتیدیلینواستیل-3-کینازpolymorphonuclear leukocyte - لکوسیت پلی مرفون هسته ایExtracellular matrix - ماتریکس خارج سلولیvascular cell adhesion molecule-1 - مولکول چسبندگی سلولی عروقی-1neutrophil - نوتروفیلextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیfocal adhesion kinase - کیناز چسبندگی کانونی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Integrin signaling is comprised of well-characterized pathways generally involved in cell survival. α9β1 integrin has recently become a target of study and has been shown to present pro-survival effects on neutrophils. However, there are no detailed studies on how α9β1 integrin-coupled signaling pathways interact and how they converge to finally modulate spontaneous apoptosis in neutrophils. In this regard we sought to investigate the main signaling events triggered by α9β1 integrin engagement and how these signaling pathways modulate the apoptotic program of human neutrophils. Using VLO5, a snake venom disintegrin shown to bind to α9β1 integrin in neutrophils, we demonstrate that α9β1 integrin engagement leads to the activation of integrin signaling pathways and potently reduces neutrophil spontaneous apoptosis. These effects are dependent on the activation of PI3K and MAPK pathways, since both LY294002 (PI3K inhibitor) or PD95059 (MEK inhibitor) reverted the effects of VLO5/α9β1 interaction. Moreover we show that VLO5/α9β1 engagement induces NF-κB nuclear translocation and increases the ratio between anti- and pro-apoptotic proteins by inducing the degradation of pro-apoptotic protein Bad and increasing the expression of anti-apoptotic protein Bcl-xL. VLO5 also inhibited the early steps of neutrophil spontaneous apoptosis by preventing Bax translocation to the outer mitochondrial membrane and consequent cytochrome c release. In conclusion, as the mechanistic details of α9β1 integrin signaling pathways in human neutrophils becomes clearer, it should become possible to develop new therapeutic agents for human diseases where neutrophils play a prominent role.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1803, Issue 7, July 2010, Pages 848-857
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1803, Issue 7, July 2010, Pages 848-857
نویسندگان
Roberta F. Saldanha-Gama, João A. Moraes, Andrea Mariano-Oliveira, Ana Lucia Coelho, Erin M. Walsh, Cezary Marcinkiewicz, Christina Barja-Fidalgo,