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α-Cyperone Inhibits PMA-Induced EPCR Shedding Through PKC Pathway

Yu Ma, Yi Zhao, Ran Zhang, Xiaoxia Liang, Zhongqiong Yin, Yi Geng, Gang Shu, Xu Song, Yuanfeng Zou, Lixia Li, Lizi Yin, Guizhou Yue, Yinglun Li, Gang Ye, Changliang He

Biol Pharm Bull. 2017 Oct 1;40(10):1678-1685.

PMID: 28804104

Abstract:

α-Cyperone, a sesquiterpene compound represents 25.23% of the total oil and is the most abundant compound in Cyperus rotundus oil. Endothelial cell protein C receptor (EPCR) is a main member in protein C (PC) anti-coagulation system. EPCR could be shed from cell surface, and is mediated by tumor necrosis factor-α converting enzyme (TACE). Nothing that EPCR is a marker of vascular barrier integrity in vascular inflammatory disease and takes part in systemic inflammatory disease. In this study, we investigated whether α-cyperone could inhibit EPCR shedding. To observe the effect, we investigated this issue by detection the effect of α-cyperone on phorbol-12-myristate 13-acetate (PMA)-induced EPCR shedding in human umbilical vein endothelial cells (HUVECs). The cells were pretreated with α-cyperone for 12 h, and then stimulated by PMA for 1 h. The solute EPCR (sEPCR) and expression of membrane EPCR (mEPCR) were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. The mRNA, protein level and activity of TACE were tested by quantitative (q)RT-PCR, Western blot and InnoZyme TACE activity assay kit. Furthermore, we measured the protein level of mitogen-activated protein kinase (MAPK) signaling and protein kinase C (PKC) pathway under this condition by Western blot. The results showed that α-cyperone could suppress PMA-induced EPCR shedding through inhibiting the expression and activity of TACE. In addition, α-cyperone could inhibit PKC translocation, but not have an effect on phosphorylation of c-Jun N-terminal kinase (JNK), p38 and extracellular regulated protein kinases (ERK) 1/2. Given these results, α-cyperone inhibits PMA-induced EPCR shedding through PKC pathway, which will provide an experimental basis for further research on α-cyperone.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP473085 α-Cyperone α-Cyperone 473-08-5 Price
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