Your browser doesn't support javascript.
loading
Reversal of phosphate-induced ORAI1 expression, store-operated Ca2+ entry and osteogenic signaling by MgCl2 in human aortic smooth muscle cells.
Zhu, Xuexue; Ma, Ke; Zhou, Kuo; Voelkl, Jakob; Alesutan, Ioana; Leibrock, Christina; Nürnberg, Bernd; Lang, Florian.
Afiliación
  • Zhu X; Department of Pharmacology, Experimental Therapy & Toxicology, Eberhard-Karls-University of Tübingen, Germany.
  • Ma K; Department of Pharmacology, Experimental Therapy & Toxicology, Eberhard-Karls-University of Tübingen, Germany.
  • Zhou K; Department of Pharmacology, Experimental Therapy & Toxicology, Eberhard-Karls-University of Tübingen, Germany.
  • Voelkl J; Institute for Physiology, Johannes-Kepler-University Linz, Austria.
  • Alesutan I; Institute for Physiology, Johannes-Kepler-University Linz, Austria.
  • Leibrock C; Fresenius Kabi, Oberursel, Germany.
  • Nürnberg B; Department of Pharmacology, Experimental Therapy & Toxicology, Eberhard-Karls-University of Tübingen, Germany.
  • Lang F; Department of Physiology, Eberhard-Karls-University, Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
Biochem Biophys Res Commun ; 523(1): 18-24, 2020 02 26.
Article en En | MEDLINE | ID: mdl-31831178
In chronic kidney disease, renal phosphate retention leads to hyperphosphatemia with subsequent vascular osteogenic signaling and calcification. Osteogenic signaling involves up-regulation of the transcription factors CBFA1, MSX2, and SOX9, as well as alkaline phosphatase (ALP), an enzyme stimulating calcification by degrading the calcification inhibitor pyrophosphate. Stimulation of osteogenic signaling and calcification by phosphate donor ß-glycerophosphate in human aortic smooth muscle cells (HAoSMCs) is attenuated by MgCl2, an effect mimicked by Ca2+-sensing receptor agonist GdCl3. Most recent observations revealed that the effect of ß-glycerophosphate on osteogenic signaling requires ORAI1, a Ca2+-channel accomplishing store-operated Ca2+-entry (SOCE), which is stimulated by Ca2+-sensor STIM1. The present study explored whether ORAI1 and/or STIM1 expression and, thus, SOCE and osteogenic signaling in HAoSMCs are sensitive to MgCl2 and/or GdCl3. To this end, transcript levels were estimated using q-RT-PCR, protein abundance with western blotting, cytosolic Ca2+-concentration ([Ca2+]i) by Fura-2-fluorescence, and SOCE from increase of [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1  µM). As a result, 24 h exposure to ß-glycerophosphate (2 mM) significantly enhanced transcript levels of ORAI1 and STIM1 as well as SOCE, effects significantly blunted or virtually abrogated by 1.5 mM MgCl2 and by 50  µM GdCl3. In conclusion, MgCl2 and GdCl3 are powerful inhibitors of ORAI1 and STIM1 expression and store-operated Ca2+-entry, effects affecting osteogenic signalling in vascular smooth muscle cells.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Transducción de Señal / Cloruro de Magnesio / Calcio / Miocitos del Músculo Liso / Proteína ORAI1 Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Transducción de Señal / Cloruro de Magnesio / Calcio / Miocitos del Músculo Liso / Proteína ORAI1 Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos