Up-Regulation of Na+/Ca2+ Exchange in Megakaryocytes Following TGFβ1 Treatment

作者:Almilaji, Ahmad; Yan, Jing; Hosseinzadeh, Zohreh; Schmid, Evi; Gawaz, Meinrad; Lang, Florian*
来源:Cellular Physiology and Biochemistry, 2016, 39(2): 693-699.
DOI:10.1159/000445660

摘要

Background: Blood platelets are activated by increase of cytosolic Ca2+ activity ([Ca2+](i)). Ca2+ entry is accomplished in part by store operated Ca2+ entry (SOCE) involving Ca2+ release activated Ca2+-channel (CRAC) moiety rail and its regulator STIM1, which are stimulated by depletion of intracellular Ca2+ stores. An increase of [Ca2+], is terminated byexchange. The expression of both, Orail and STIM1 in megakaryocytes is up-regulated by tumor growth factor TGF beta 1, a powerful regulator of megakaryocyte differentiation. The present study explored whether TGF beta 1 similarly modifies megakaryocyte Na+/Ca2+- exchanger activity. Methods: [Ca2+](i), was determined utlizing Fura 2 fluorescence, SOCE from increase of [Call, following readdition of extracellular Ca2+ after store depletion, and Na+/Ca(2+-)exchanger activity from increase of [Ca2+](i), and whole cell currents following removal of extracellular Na+. Results: TGF beta 1 treatment not only augments the increase of [Ca2+](i) following store depletion and SOCE, but significantly up-regulates Na+/Ca2+- exchanger activity as apparent from [Call measurements and whole cell currents. Conclusions: TGF beta 1 is a powerful stimulator of both, SOCE and Na+/Ca2+- exchanger activity in megakaryocytes.