Evidence for the formation of a novel cyclopentenone isoprostane, 15-A(2t)-isoprostane (8-iso-prostaglandin A(2)) in vivo

A(2)/J(2)-Isoprostanes (IsoPs) are prostaglandin (PG) A(2)/J(2)-like compou nds that are produced in vivo as dehydration products of D-2/E-2/-IsoPs. On e A(2)-IsoP that should be formed is 15-A(2t)-IsoP (8-iso-PGA(2)). Analogou s to cyclopentenone PGs, 15-A(2t)-IsoP readily undergoes nucleophilic addit ion to various biomolecules suggesting the compound is capable of exerting potent bioactivity. However, proof that it is definitively formed in vivo i s lacking. Evidence is now presented that 15-A(2t)-IsoP, in fact, is genera ted in vivo by demonstrating that an endogenous A(2)-IsoP with a retention time on capillary GC identical with that 15-A(2t)-IsoP co-chromatographs th rough four high resolving HPLC purification procedures with authentic radio labeled 15-A(2t)-IsoP. (C) 1999 Elsevier Science B.V. All rights reserved.