کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8302582 | 1537740 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts
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کلمات کلیدی
DNA-damage-inducible transcript 3hydroperoxy-eicosatetraenoic acidSenescence associated-β-galactosidasePGH2mPGESDcR2PGTNHDFsSA-β-galMCP1DCFDACOX-2PPARHUVECSPGE2ROS - ROSinterleukin - اینترلوکینOxidative stress - تنش اکسیداتیوPopulation doubling - جمعیت دو برابر می شودdichlorofluorescein diacetate - دی کللت فلوئورسین دی سکتهHuman umbilical vascular endothelial cells - سلول های اندوتلیال عروق انسانی انسانیcyclooxygenase 2 - سیکلوکوکسیژناز 2normal human dermal fibroblasts - فیبروبلاست های طبیعی پوست انسانHPETE - هتلیmonocyte chemoattractant protein-1 - پروتئین شیمیایی monocyte chemoattractant-1prostaglandin E receptor - پروستاگلاندین E receptorprostaglandin E synthase - پروستاگلاندین E سنتازProstaglandin E2 - پروستاگلاندین E2Prostaglandin H2 - پروستاگلاندین H2prostaglandin transporter - پروستاگلاندین حمل کنندهSenescence - پیریReactive oxygen species - گونههای فعال اکسیژنEP receptor - گیرنده EPperoxisome proliferator-activated receptor - گیرنده فعال فعال پروکسیوم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cyclooxygenase 2 and release of prostaglandin E2 are involved in many responses including inflammation and are upregulated during cellular senescence. However, little is known about the role of lipid inflammatory mediators in senescence. Here, we investigated the mechanism by which the COX-2/PGE2 axis induces senescence. Using the NS398 specific inhibitor of COX-2, we provide evidence that reactive oxygen species by-produced by the COX-2 enzymatic activity are negligible in front of the total senescence-associated oxidative stress. We therefore investigated the role of PGE2 by invalidating the PGE2 synthases downstream of COX-2, or the specific PGE2 receptors, or by applying PGE2 or specific agonists or antagonists. We evaluated the effect on senescence by evaluating the senescence-associated proliferation arrest, the percentage of senescence-associated β-galactosidase-positive cells, and the expression of senescent molecular markers such as IL-6 and MCP1. We show that PGE2 acting on its EP specific receptors is able to induce both the onset of senescence and the maintenance of the phenotype. It did so only when the PGE2/lactate transporter activity was enhanced, indicating that PGE2 acts on senescence more via the pool of intracellular EP receptors than via those localized at the cell surface. Treatment with agonists, antagonists and silencing of the EP receptors by siRNA revealed that EP3 was the most involved in transducing the intracrine effects of PGE2. Immunofluorescence experiments confirmed that EP3 was more localized in the cytoplasm than at the cell surface. Taken together, these results suggest that COX-2 contributes to the establishment and maintenance of senescence of normal human fibroblasts via an independent-ROS and a dependent-PGE2/EPs intracrine pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1831, Issue 7, July 2013, Pages 1217-1227
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1831, Issue 7, July 2013, Pages 1217-1227
نویسندگان
Sébastien Martien, Olivier Pluquet, Chantal Vercamer, Nicolas Malaquin, Nathalie Martin, Karo Gosselin, Albin Pourtier, Corinne Abbadie,