J Mol Med DOI 10.1007/s00109-014-1234-2

ORIGINAL ARTICLE

High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling Nikoleta Daskoulidou & Bo Zeng & Lisa M. Berglund & Hongni Jiang & Gui-Lan Chen & Olga Kotova & Sunil Bhandari & James Ayoola & Steven Griffin & Stephen L. Atkin & Maria F. Gomez & Shang-Zhong Xu

Received: 1 August 2014 / Revised: 6 November 2014 / Accepted: 19 November 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract ORAI and stromal interaction molecule (STIM) are storeoperated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca2+ store to Ca2+ influx. However, the roles of ORAI and STIM in vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM D-glucose), which was accompanied by enhanced store-operated Ca2+ influx in vascular endothelial cells. The increased expression was also observed in Electronic supplementary material The online version of this article (doi:10.1007/s00109-014-1234-2) contains supplementary material, which is available to authorized users. N. Daskoulidou : B. Zeng : H. Jiang : G.

STIM via calcineurin-NFAT signalling.

ORAI and stromal interaction molecule (STIM) are store-operated channel molecules that play essential roles in human physiology through a coupling mec...
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