کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2144821 1088622 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells
چکیده انگلیسی

A novel Kunitz-type serine proteinase inhibitor, termed PIVL, was purified to homogeneity from the venom of the Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric polypeptide chain cross-linked by three disulfide linkages with an isotope-averaged molecular mass of 7691.7 Da. The 67-residue full-length PIVL sequence was deduced from a venom gland cDNA clone. Structurally, PIVL is built by a single Kunitz/BPTI-like domain. Functionally, it is able to specifically inhibit trypsin activity. Interestingly, PIVL exhibits an anti-tumor effect and displays integrin inhibitory activity without being cytotoxic. Here we show that PIVL is able to dose-dependently inhibit the adhesion, migration and invasion of human glioblastoma U87 cells. Our results also show that PIVL impairs the function of αvβ3 and to a lesser extent, the activity of αvβ6, αvβ5, α1β1 and α5β1 integrins. Interestingly, we demonstrate that the 41RGN43 motif of PIVL is likely responsible for its anti-cancer effect. By using time lapse videomicroscopy, we found that PIVL significantly reduced U87 cells motility and affected cell directionality persistence by 68%. These findings reveal novel pharmacological effects for a Kunitz-type serine proteinase inhibitor.


► PIVL, a new serine protease inhibitor was isolated from snake venom.
► It was able to inhibit specifically trypsin activity.
► PIVL exhibited an anti-tumor effect and displayed an anti-integrin activity.
► We demonstrate that the 41RGN43 motif of PIVL is likely responsible for this effect.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volume 32, Issue 1, January 2013, Pages 52–62
نویسندگان
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