Impairment of phosphatidylinositol signaling in acetylshikonin-treated neutrophils

CMUR > College of Pharmacy > Graduate Institute of Pharmaceutical Chemistry > Journal articles > Item 310903500/30930

Please use this identifier to cite or link to this item: http://ir.cmu.edu.tw/ir/handle/310903500/30930

Title:	Impairment of phosphatidylinositol signaling in acetylshikonin-treated neutrophils
Authors:	Wang, JP;Kuo, SC
Contributors:	藥學院藥化所;CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG,TAIWAN
Date:	1997
Issue Date:	2010-09-24 15:06:42 (UTC+8)
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Abstract:	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.
Relation:	BIOCHEMICAL PHARMACOLOGY 53(8):1173-1177
Appears in Collections:	[Graduate Institute of Pharmaceutical Chemistry] Journal articles

Files in This Item:

There are no files associated with this item.

Loading...