کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568929 1128498 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom
چکیده انگلیسی


• Isolation of three novel snake venom CLPs inhibiting α2β1 integrin
• Reporting hexameric CLP, sochicetin-A with anti-collagen receptor activity
• CLPs antagonize the interaction of glioma cells with collagen matrix.
• Sochicetin-A does not support glioma cell spreading.

Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ)3 in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 269, Issue 1, 15 May 2013, Pages 34–42
نویسندگان
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