title: Novel priming compounds of cystathionine metabolites on superoxide generation in human neutrophils.
abstract: 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-(3-oxo-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 12-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.
authors.affiliation: Department of Chemistry, Kochi Medical School, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kodama
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D003540:Cystathionine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; C110306:N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine; D013481:Superoxides; D003540:Cystathionine; D014443:Tyrosine; C010094:cystathionine sulfoxide; C038681:cystathionine ketimine