The arachidonate-dependent cytoprotective signaling evoked by peroxynitrite is a general response of the monocyte/macrophage lineage.
U937, THP-1, and J774 cells or human monocytes and macrophages display similar levels of sensitivity to peroxynitrite and exposure to an otherwise non-toxic concentration of the oxidant in the presence of a phospholipase A(2) inhibitor was invariably associated with the onset of mitochondrial permeability transition (MPT)-dependent toxicity. These events were prevented by exogenous arachidonic acid (AA). In general, the protective concentrations of AA were greater in those cell types releasing more AA. Thus, non-toxic concentrations of peroxynitrite commit cells belonging to the monocyte/macrophage lineage to MPT-dependent toxicity that is however prevented by endogenous AA.
Tommasini
Ilaria
I
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo," Via S. Chiara, 27-61029 Urbino, PU, Italy.
Guidarelli
Andrea
A
Cerioni
Liana
L
Cantoni
Orazio
O
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000633:toxicity*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
D030421:Peroxynitrous Acid; D016718:Arachidonic Acid