Evidence for the involvement of protein kinase C inhibition by norathyriol in the reduction of phorbol ester-induced neutrophil superoxide anion generation and aggregation

被引:19
作者
Wang, JP [1 ]
Raung, SL [1 ]
Tsao, LT [1 ]
Lin, CN [1 ]
机构
[1] KAOHSIUNG MED COLL,SCH PHARM,KAOHSIUNG,TAIWAN
关键词
norathyriol; neutrophil; rat; respiratory burst; aggregation; protein kinase C; phorbol; 12-myristate; 13-acetate; translocation;
D O I
10.1016/S0014-2999(97)01214-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Norathyriol, a xanthone aglycone, inhibited superoxide anion (O-2(-)) generation and O-2 consumption in phorbol 12-myristate 13-acetate (PMA)-activated rat neutrophils in a concentration-dependent manner. In addition, norathyriol inhibited PMA-but enhanced formylmethionyl-leucyl-phenylalanine (fMLP)-induced neutrophil aggregation. Norathyriol suppressed neutrophil cytosolic protein kinase C as well as rat brain protein kinase C over the same range of concentrations at which it inhibited the respiratory burst. Norathyriol did not affect [H-3]phorbol 12,13-dibutyrate ([H-3]PDB) binding to neutrophil cytosolic protein kinase C, but effectively attenuated trypsin-treated rat brain protein kinase C activity. Moreover, norathyriol was found to be a noncompetitive inhibitor with respect to ATP and peptide substrate (N-terminal acetylated, amino acid sequence 4-14 of the myelin basic protein, Ac-MBP-(4-14)). Unlike staurosporine, norathyriol did not affect porcine heart protein kinase A activity. On the immunoblot analysis of protein kinase C subcellular distribution, the PMA-induced translocation of protein kinase C-beta from the cytosol to the membrane was not affected by norathyriol. These results show that the inhibition by a plant product, norathyriol, of PMA-induced respiratory burst and aggregation is, at least pastry, attributed to the direct suppression of protein kinase C activity through blockade of the catalytic region, but is not due to interference with the membrane translocation of protein kinase C during PMA-induced cell activation. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:81 / 88
页数:8
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