کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7270831 | 1473241 | 2009 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Rac GTPase-activating bacterial protein toxin CNF1 induces analgesia up-regulating μ-opioid receptors
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کلمات کلیدی
CNF1Intraplantari.pl.i.p.ICVintracerebroventricularPAGRho GTPasesperiaqueductal gray - خاکستری پرآبیintraperitoneal - داخل صفاقیPain - دردBehavior - رفتارCytotoxic Necrotizing Factor 1 - فاکتور نکروتیزی سیتوتوکسیک 1MORs - مورسMice - موشCytoskeleton - چارچوب یاخته، سیتواسکلتون، اسکلت سلولیRho-associated kinase - کیناز وابسته به Rhoμ-opioid receptors - گیرنده های μ-opioidRock - یا راک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin from Escherichia coli that constitutively activates the Rho, Rac and Cdc42 GTPases. These regulatory proteins oscillate between a cytosolic GDP-bound inactive form and a membrane-linked GTP-bound active form, orchestrating the actin cytoskeleton assembly and dynamics. We herein describe, for the first time, the ability of CNF1 to potently counteract the formalin-induced inflammatory pain in mice. The analgesic response due to CNF1 requires both the sustained activation of the Rac GTPase, with consequent cerebral actin cytoskeleton remodeling, and the up-regulation of the μ-opioid receptors (MORs), the most important receptors controlling pain perception. The crucial role of Rac is proved by the lack of analgesic activity in mice challenged with a recombinant CNF1, in which the enzymatic activity was abolished by substituting serine with cysteine at position 866. The importance of MORs is proved by the inability of CNF1 to induce any analgesic effect in MORs knockout mice and by the ability of naloxone to antagonize the analgesic effects. Furthermore, it is worth noting that the analgesic effect in mice occurs after both peripheral and central administration of CNF1. Hence, taken altogether, our findings provide new insights into the comprehension of intracellular mechanisms involved in pain modulation, and indicate this bacterial protein toxin as a novel tool in the field of pain control. Conceivably, this might pave the way for new therapeutic strategies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN® - Volume 145, Issues 1â2, September 2009, Pages 219-229
Journal: PAIN® - Volume 145, Issues 1â2, September 2009, Pages 219-229
نویسندگان
Flaminia Pavone, Siro Luvisetto, Sara Marinelli, Elisabetta Straface, Alessia Fabbri, Loredana Falzano, Carla Fiorentini, Walter Malorni,