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Tetramethylpyrazine reduces intra‐platelet calcium via suppressing the SGK1/STIM1/Orai1 pathway
Author(s) -
Wang Zhentao,
Cang Hongbo,
Gao Shuibo,
Han Lihua,
Wu Hong
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.677.1
Subject(s) - orai1 , chemistry , stimulation , pharmacology , platelet , stim1 , western blot , medicine , calcium , biochemistry , gene
Tetramethylpyrazine (TMPZ) is frequently administered for cardiovascular diseases. Although TMPZ is thought to inhibit the elevation of intra‐platelet calcium ions (Ca2+), the underlying mechanism remains unknown. Herein, the time‐dependent effect of TMPZ on adenosine diphosphate (ADP)‐induced platelet aggregation was assessed using a turbidimetric approach. Meanwhile, the intracellular Ca2+ concentration following ADP stimulation was determined using a fluo‐4 Ca2+ probe. We then clarified the mechanisms underlying TMPZ intervention by determining the mRNA and protein levels of Ca2+‐related pathway including stromal interaction molecule l (STIM1), Orai1, and serum/glucocorticoid‐regulated protein kinase 1 (SGK1) by real‐time PCR and Western blot, respectively. The results showed that TMPZ significantly reduced platelet aggregation in a dose‐dependent manner. In addition, TMPZ markedly decreased intracellular Ca2+ concentration following ADP stimulation. Treatment with 2‐mM TMPZ inhibited ADP‐induced expression of STIM1 and Orai1 in platelets at both the mRNA and protein levels, and also reduced the expression of the SGK1 protein. In summary, TMPZ reduces the intra‐platelet Ca2+, which then inhibits platelet activation and thrombosis. The underlying mechanism is presumed to be through the suppression of the SGK1/STIM1/Orai1 pathway. Support or Funding Information This work was supported by grants from the Scientific Research Foundation for the Returned Oversea Chinese Scholars, State Ministry of Education of China and Collaborative Innovation Center of Henan University of Traditional Chinese Medicine