Novel priming compounds of cystathionine metabolites on superoxide generation in human neutrophils
Novel priming compounds of cystathionine metabolites on superoxide generation in human neutrophils
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DOI：
10.1006/bbrc.1999.1970
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发表时间：
2000-03-16
影响因子：
3.1
通讯作者：
Sugahara, K
中科院分区：
文献类型：
--
作者：
Kodama, H;Zhang, JY;Sugahara, K
将人外周血多形核白细胞与胱硫醚尿症患者尿液中发现的胱硫醚和胱硫醚代谢物预孵育。在胱硫醚代谢产物中，胱硫醚酮亚胺和N-乙酰基-S-（3-氧代-3-羧基-正丙基）半胱氨酸（NAc-OCPC）显著增强N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）诱导的超氧化物生成，但胱硫醚，NAc-胱硫醚和环硫醚没有增强超氧化物生成。胱硫醚酮亚胺和NAc-OCPC也增强了调理酵母聚糖（OZ）诱导的超氧阴离子产生，但对花生四烯酸（AA）和佛波酯（PMA）诱导的超氧阴离子产生无明显影响。酪氨酸激酶抑制剂genistein可抑制cystathioketimine和NAc-OCPC诱导的超氧化物生成，而蛋白激酶C抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（H-7）可增强cystathioketimine和NAc-OCPC诱导的超氧化物生成。胱硫醚酮亚胺和NAc-OCPC也显着增加人中性粒细胞中45 kDa蛋白的磷酸化，磷酸化依赖于胱硫醚酮亚胺和NAc-OCPC的浓度。酪氨酸激酶抑制剂genistein和除莠霉素A可抑制胱硫醚酮亚胺和NAc-OCPC诱导的45-kDa蛋白磷酸化，而蛋白激酶C抑制剂H-7和staurosporine则不抑制。胱硫醚代谢物和L-胱硫醚亚砜被分离成两种非对映异构体，CS-I和CS-II。CS-I能增强AA和PMA诱导的超氧阴离子产生，但对fMLP和OZ诱导的超氧阴离子产生无明显影响。相反，CS-II增强fMLP和OZ诱导的超氧阴离子产生，但不增强AA和PMA诱导的超氧阴离子产生。(C)北京大学出版社.
Human peripheral blood polymorphonuclear leukocytes were preincubated with cystathionine and cystathionine metabolites found in the urine of patients with cystathioninuria. Among the cystathionine metabolites, cystathionine ketimine and N-acetyl-S-(3oxo-3-carboxy-n-propyl) cysteine (NAc-OCPC) significantly enhanced the N-formylmethionylleucylphenylalanine (fMLP)-induced superoxide generation, but cystathionine, NAc-cystathionine, and cyclothionine did not enhance the superoxide generation. Cystathionine ketimine and NAc-OCPC also enhanced superoxide generation induced by opsonized zymosan (OZ) but not that induced by arachidonic acid (AA) and phorbol la-myristate 13-acetate (PMA). Superoxide generation induced by cystathionine ketimine and NAc-OCPC was inhibited by genistein, an inhibitor of tyrosine kinase, and was enhanced by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. Cystathionine ketimine and NAc-OCPC markedly also increased phosphorylation of 45-kDa protein in human neutrophils and the phosphorylation depended on the concentrations of cystathionine ketimine and NAc-OCPC. The phosphorylation of 45-kDa protein induced by cystathionine ketimine and NAc-OCPC was inhibited by genistein and herbimycin A, inhibitors of tyrosine kinase, but was not inhibited by H-7 and staurosporine, inhibitors of protein kinase C. Cystathionine metabolites and L-cystathionine sulfoxides were separated into two diastereoisomers, CS-I and CS-II. CS-I enhanced the superoxide generation induced by AA and PMA but not that induced by fMLP and OZ. In contrast, CS-II enhanced the superoxide generation induced by fMLP and OZ, but not that induced by AA and PMA. (C) 2000 Academic Press.