کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201787 1100039 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nav1.7 sodium channel-induced Ca2+ influx decreases tau phosphorylation via glycogen synthase kinase-3β in adrenal chromaffin cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Nav1.7 sodium channel-induced Ca2+ influx decreases tau phosphorylation via glycogen synthase kinase-3β in adrenal chromaffin cells
چکیده انگلیسی

In cultured bovine adrenal chromaffin cells expressing Nav1.7 sodium channel isoform, veratridine increased Ser473-phosphorylation of Akt and Ser9-phosphorylation of glycogen synthase kinase-3β by ∼217 and ∼195%, while decreasing Ser396-phosphorylation of tau by ∼36% in a concentration (EC50 = 2.1 μM)- and time (t1/2 = 2.7 min)-dependent manner. These effects of veratridine were abolished by tetrodotoxin or extracellular Ca2+ removal. Veratridine (10 μM for 5 min) increased translocation of Ca2+-dependent conventional protein kinase C-α from cytoplasm to membranes by 47%; it was abolished by tetrodotoxin, extracellular Ca2+ removal, or Gö6976 (an inhibitor of protein kinase C-α), and partially attenuated by LY294002 (an inhibitor of phosphatidylinositol 3-kinase). LY294002 (but not Gö6976) abrogated veratridine-induced Akt phosphorylation. In contrast, either LY294002 or Gö6976 alone attenuated veratridine-induced glycogen synthase kinase-3β phosphorylation by 65 or 42%; however, LY294002 plus Gö6976 completely blocked it. Veratridine (10 μM for 5 min)-induced decrease of tau phosphorylation was partially attenuated by LY294002 or Gö6976, but completely blocked by LY294002 plus Gö6976; okadaic acid or cyclosporin A (inhibitors of protein phosphatases 1, 2A, and 2B) failed to alter tau phosphorylation. These results suggest that Na+ influx via Nav1.7 sodium channel and the subsequent Ca2+ influx via voltage-dependent calcium channel activated (1) Ca2+/protein kinase C-α pathway, as well as (2) Ca2+/phosphatidylinositol 3-kinase/Akt and (3) Ca2+/phosphatidylinositol 3-kinase/protein kinase C-α pathways; these parallel pathways converged on inhibitory phosphorylation of glycogen synthase kinase-3β, decreasing tau phosphorylation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 54, Issue 8, July 2009, Pages 497–505
نویسندگان
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