کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2512449 1118355 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of STIM1 phosphorylation underlies resveratrol-induced inhibition of store-operated calcium entry
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Inhibition of STIM1 phosphorylation underlies resveratrol-induced inhibition of store-operated calcium entry
چکیده انگلیسی

Resveratrol, a natural phytoalexin that shows health-promoting benefits, is an inhibitor of store-operated calcium entry (SOCE). Knowledge of the molecular mechanism underlying this inhibition is required for the proper design of therapies that include resveratrol or related stilbenoids, but remains largely unknown. To unravel this mechanism, using HEK293 cells as a model, we found that resveratrol inhibited the ERK1/2 activation triggered by Ca2+ store depletion. As a consequence, resveratrol inhibited STIM1 phosphorylation at residues Ser575, Ser608, and Ser621. Because this phosphorylation regulates the dissociation of STIM1 from the microtubule plus-end binding protein EB1 under store depletion conditions, resveratrol inhibited STIM1-EB1 dissociation. This inhibition had downstream effects such as inhibition of STIM1 multimerization in response to store depletion, and a significant impairment in the binding of STIM1 to ORAI1. Although additional targets for resveratrol in the molecular mechanism that governs SOCE cannot be discarded, the present results demonstrate that ERK1/2 pathway is a major target for resveratrol, and that the impairment of its activation produces a significant inhibition of SOCE.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 86, Issue 11, 1 December 2013, Pages 1555–1563
نویسندگان
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