title: Differential selectivity of protein modification by the cyclopentenone prostaglandins PGA1 and 15-deoxy-Delta12,14-PGJ2: role of glutathione.
abstract: Cyclopentenone prostaglandins (cyPG) with antiinflammatory and antiproliferative properties have been envisaged as leads for the development of therapeutic agents. Because cyPG effects are mediated in part by the formation of covalent adducts with critical signaling proteins, it is important to assess the specificity of this interaction. By using biotinylated derivatives of 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)-B) and PGA(1) (PGA(1)-B) we herein provide novel evidence for the differential selectivity of protein modification by distinct cyPG. The marked quantitative and qualitative differences in the binding of 15d-PGJ(2)-B and PGA(1)-B to cellular proteins were related to a differential reactivity in the presence of glutathione (GSH), both in vitro and in intact cells. Therefore GSH levels may influence not only the intensity but also the specificity of cyPG action.
authors.affiliation: Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gayarre
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stamatakis
authors.forename: Marta
authors.initials: M
authors.lastname: Renedo
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez-Sala
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology*; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D011454:Prostaglandins A; D011506:Proteins; D005978:Glutathione; C013905:cyclopentenone; D015230:Prostaglandin D2; C100573:prostaglandin A1