中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/30930
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    題名: Impairment of phosphatidylinositol signaling in acetylshikonin-treated neutrophils
    作者: Wang, JP;Kuo, SC
    貢獻者: 藥學院藥化所;CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG,TAIWAN
    日期: 1997
    上傳時間: 2010-09-24 15:06:42 (UTC+8)
    出版者: PERGAMON-ELSEVIER SCIENCE LTD
    摘要: Cycloheterophyllin, a prenylflavone, inhibited the superoxide anion (O-2(.-)) generation from formyl-methionyl-leucyl-phenylalanine (fMLP)- and phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils in a concentration-dependent manner with IC50 values of 47.0 +/- 5.0 and 1.7 +/- 0.4 mu M, respectively. Cycloheterophyllin had no effect on O-2(.-) generation in xanthine-xanthine oxidase system and during dihydroxyfumaric acid (DHF) autoxidation. Cycloheterophyllin exerted a concentration-dependent inhibition of neutrophil cytosolic protein kinase C (PKC) and rat brain PKC, but had no effect on porcine heart protein kinase A (PKA). Unlike staurosporine, cycloheterophyllin did not affect the trypsin-treated rat brain PKC. [H-3]Phorbol 12,13-dibutyrate ([H-3]PDB) binding to neutrophil cytosolic PKC was significantly suppressed by cycloheterophyllin. However, cycloheterophyllin had negligible effect on the PMA-induced membrane translocation of PKC-beta and PKC-delta in neutrophils, Moreover, the fMLP-induced [Ca2+](i) elevation and inositol trisphosphate (IP3) formation of neutrophils were not affected by cycloheterophyllin at concentrations which significantly suppressed the O-2(.-) generation. In cell-free system, addition of arachidonate (AA) into the mixture of cytosol and membrane fractions of the resting neutrophils to make NADPH oxidase assembly and activation. Cycloheterophyllin had no effect on O-2(.-) generation in AA-activated cell-free system. These results suggest that the suppression of PKC activity through the interaction with the regulatory region of PKC is involved in the inhibition by cycloheterophyllin of the O-2(.-) generation in rat neutrophils.
    關聯: BIOCHEMICAL PHARMACOLOGY 53(8):1173-1177
    顯示於類別:[藥物化學研究所] 期刊論文

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