The marine toxin okadaic acid reduces O2- generation and tyrosine phosphorylation in LPS-primed rat neutrophils.
Contrasting effects of okadaic acid (OKA) on neutrophil (PMN) superoxide anion (O2-) generation have been reported. In this study, we examined the effect of OKA on phorbol myristate acetate (PMA)-stimulated O2- generation in rat PMNs primed with LPS in vivo (LPS-PMN) and saline-treated rat PMNs (SAL-PMN). The following results were observed: (1) OKA, but neither genistein nor vanadate, markedly reduced O2- generation in a dose and time-dependent manner; (2) genistein, a tyrosine kinase inhibitor, as well as OKA, reduced tyrosine phosphorylation; (3) sodium orthovanadate, a tyrosine phosphatase inhibitor, potently enhanced tyrosine phosphorylation. Our studies suggest that OKA might reduce tyrosine phosphorylation by affecting the activity of tyrosine phosphatases regulated by serine-threonine phosphorylation.
Mayer
A M
AM
Midwestern University, Department of Pharmacology, Downers Grove, IL 60515, USA. amayer@midwestern.edu
Choudhry
M A
MA
Sayeed
M M
MM
Spitzer
J A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019319:Okadaic Acid; D014443:Tyrosine; D010100:Oxygen