INHIBITION BY GOMISIN-C (A LIGNAN FROM SCHIZANDRA-CHINENSIS) OF THE RESPIRATORY BURST OF RAT NEUTROPHILS
INHIBITION BY GOMISIN-C (A LIGNAN FROM SCHIZANDRA-CHINENSIS) OF THE RESPIRATORY BURST OF RAT NEUTROPHILS
复制标题
DOI：
10.1111/j.1476-5381.1994.tb17084.x
复制
发表时间：
1994-11-01
影响因子：
7.3
通讯作者：
CHEN, CC
中科院分区：
文献类型：
--
作者：
WANG, JP;RAUNG, SL;CHEN, CC
1探讨了戈米辛C抑制体外培养的大鼠中性粒细胞呼吸爆发的可能机制。2肽甲酰-蛋氨酸-亮氨酸-苯丙氨酸（FMLP）诱导的超氧阴离子（O-2（.-））Gomisin C以浓度依赖性方式抑制O-2的形成和O-2消耗（O-2（.-）的IC 50为21.5 +/- 4.2 μ g ml（-1））形成）。Gomisin C也抑制O-2（.-）在低浓度的佛波醇肉豆蔻酸酯乙酸酯（PMA）下，O-2（.-）的IC 50值为26.9 +/- 2.1 μ g ml（-1），阵然而，gomisin C并不影响高浓度PMA诱导的反应。黄嘌呤-黄嘌呤氧化酶系统中的O-2（.-）与三氟拉嗪（TFP）一样，戈米辛C以浓度依赖性方式减弱PMA激活的中性粒细胞颗粒NADPH氧化酶的活性。5戈米辛C在存在或不存在EDTA的情况下降低FMLP刺激的中性粒细胞中胞浆游离Ca 2+的升高。环匹阿尼酸（CPA）可诱导胞内钙库释放，戈米辛C也可抑制CPA的释放。而戈米辛C对CPA激活的Ca ~（2+）内流通路无影响。6毛喉素能显著增加细胞内cAMP水平，而戈米辛C对cAMP水平无影响。此外，FMLP激活的中性粒细胞中的磷酸肌醇水平不受戈米辛C的影响。7这些结果表明，戈米辛C对呼吸爆发的抑制作用不是由细胞环AMP或磷酸肌醇的变化介导的，也不是由清除O-2（.-）从嗜中性粒细胞释放，但可能介导的部分抑制NADPH氧化酶和部分减少胞质Ca 2+释放从激动剂敏感的细胞内存储。
1 The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated.2 The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O-2(.-)) formation and O-2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (IC50 21.5 +/- 4.2 mu g ml(-1) for O-2(.-) formation). Gomisin C also suppressed O-2(.-) formation and O-2 consumption at low concentrations of phorbol myristate acetate (PMA) with an IC50 value of 26.9 +/- 2.1 mu g ml(-1) for O-2(.-) formation. However, gomisin C did not affect the responses induced by a high concentration of PMA.3 Gomisin C had no effect on O-2(.-) generation and uric acid formation in the xanthine-xanthine oxidase system, and failed to alter O-2(.-) generation during dihydroxyfumaric acid (DHF) autoxidation, indicating that it does not scavenge superoxide.4 Like trifluoperazine (TFP), gomisin C attenuated the activity of PMA-activated neutrophil particulate NADPH oxidase in a concentration-dependent manner.5 Gomisin C reduced the elevations of cytosolic free Ca2+ in neutrophils stimulated by FMLP in the presence or absence of EDTA. Cyclopiazonic acid (CPA) induced the release of Ca2+ from intracellular stores and this was also reduced by gomisin C. However, the Ca2+ influx pathway activated by CPA was not affected by gomisin C.6 The cellular cyclic AMP level was markedly increased by forskolin, but not by gomisin C. Moreover, the inositol phosphate levels in FMLP-activated neutrophils were not affected by gomisin C.7 These results show that the inhibitory action of gomisin C on the respiratory burst is not mediated by changes in cellular cyclic AMP or in inositol phosphates, or by scavenging O-2(.-) released from neutrophils, but may be mediated partly by the suppression of NADPH oxidase and partly by the decrease of cytosolic Ca2+ released from an agonist-sensitive intracellular store.