Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide generation in human neutrophils.
Human peripheral blood polymorphonuclear leukocytes were preincubated with lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in normal human urine and bovine brain. Among these compounds, lanthionine ketimine and to a lesser extent S-(2-aminoethyl)- L-cysteine ketimine enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl phosphorylation was markedly increased with time, and the phosphorylation process was dependent on the concentration of both ketimines. However, lanthionine, 1,4-thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4-thiomorpholine-3-carboxylic acid were without effect both on superoxide generation and on tyrosyl phosphorylation of 45 kDa protein. Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation induced by opsonized zymosan but not the one induced by arachidonic acid and phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2- methylpiperazine, an inhibitor of protein kinase C.
Zhang
J
J
Department of Chemistry, Kochi Medical School, Japan.
Sugahara
K
K
Hashimoto
K
K
Sagara
Y
Y
Fontana
M
M
Duprè
S
S
Kodama
H
H
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000603:Amino Acids, Sulfur; D001798:Blood Proteins; D004791:Enzyme Inhibitors; D013481:Superoxides; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C035497:thialysine ketimine; C035499:lanthionine ketimine; D019833:Genistein; D009245:NADH Dehydrogenase