Involvement of STIM1 in the proteinase-activated receptor 1-mediated Ca2+ influx in vascular endothelial cells

Katsuya Hirano, Mayumi Hirano, Akiko Hanada

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Thrombin increases the cytosolic Ca2+ concentrations and induces NO production by activating proteinase-activated receptor 1 (PAR1) in vascular endothelial cells. The store-operated Ca2+ influx is a major Ca 2+ influx pathway in non-excitable cells including endothelial cells and it has been reported to play a role in the thrombin-induced Ca2+ signaling in endothelial cells. Recent studies have identified stromal interaction molecule 1 (STIM1) to function as a sensor of the store site Ca 2+ content, thereby regulating the store-operated Ca2+ influx. However, the functional role of STIM1 in the thrombin-induced Ca 2+ influx and NO production in endothelial cells still remains to be elucidated. Fura-2 and diaminorhodamine-4M fluorometry was utilized to evaluate the thrombin-induced changes in cytosolic Ca2+ concentrations and NO production, respectively, in porcine aortic endothelial cells transfected with small interfering RNA (siRNA) targeted to STIM1. STIM1-targeted siRNA suppressed the STIM1 expression and the thapsigargin-induced Ca2+ influx. The degree of suppression of the STIM1 expression correlated well to the degree of suppression of the Ca2+ influx. The knockdown of STIM1 was associated with a substantial inhibition of the Ca2+ influx and a partial reduction of the NO production induced by thrombin. The thrombin-induced Ca 2+ influx exhibited the similar sensitivity toward the Ca 2+ influx inhibitors to that seen with the thapsigargin-induced Ca2+ influx. The present study provides the first evidence that STIM1 plays a critical role in the PAR1-mediated Ca2+ influx and Ca 2+-dependent component of the NO production in endothelial cells.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalJournal of Cellular Biochemistry
Issue number2
Publication statusPublished - Oct 1 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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