Evidence for the formation of a novel cyclopentenone isoprostane, 15-A2t-isoprostane (8-iso-prostaglandin A2) in vivo

A(2)/J(2)-Isoprostanes (IsoPs) are prostaglandin (PG) A(2)/J(2)-like compounds that are produced in vivo as dehydration products of D-2/E-2/-IsoPs. One A(2)-IsoP that should be formed is 15-A(2t)-IsoP (8-iso-PGA(2)). Analogous to cyclopentenone PGs, 15-A(2t)-IsoP readily undergoes nucleophilic addition to various biomolecules suggesting the compound is capable of exerting potent bioactivity. However, proof that it is definitively formed in vivo is lacking. Evidence is now presented that 15-A(2t)-IsoP, in fact, is generated 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 through four high resolving HPLC purification procedures with authentic radiolabeled 15-A(2t)-IsoP. (C) 1999 Elsevier Science B.V. All rights reserved.