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: H Kodama, J Zhang, K Sugahara
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 269 Issue 2 Pg. 297-301 (Mar 16 2000) ISSN: 0006-291X [Print] United States
• PMID: 10708546 (Publication Type: Journal Article)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Amino Acids
• Carboxylic Acids
• N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine
• Superoxides
• Cystathionine
• Tyrosine
• cystathionine sulfoxide
• cystathionine ketimine

Topics

• Amino Acids (pharmacology)
• Carboxylic Acids (pharmacology)
• Cystathionine (analogs & derivatives, metabolism, pharmacology)
• Humans
• Neutrophils (drug effects, metabolism)
• Phosphorylation
• Stereoisomerism
• Superoxides (metabolism)
• Tyrosine (metabolism)