ERK1/2-dependent regulation of U937 cell survival after exposure to peroxynitrite.
A short-term growth of U937 cells in serum-free medium causes a prompt, mitochondrial permeability transition (MPT)-dependent necrotic response after exposure to an otherwise non-toxic concentration of peroxynitrite. This event is mediated by inhibition of extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, essential for the cytosolic phospholipase A(2)-dependent arachidonic acid (AA) release evoked by peroxynitrite. Reduced availability of the lipid messenger would therefore limit the efficiency of the AA-dependent survival signalling and cause an MPT-based necrosis. Since peroxynitrite further reduces the extent of ERK1/2 phosphorylation, regardless of whether cells had been grown in serum-free or -containing medium, it appears that basal ERK1/2 phosphorylation is a critical determinant for the survival response of U937 cells to a non-toxic, but nevertheless MPT-committing, concentration of peroxynitrite.
Tommasini
Ilaria
I
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo," Via S. Chiara, 27-61029 Urbino (PU), Italy.
Cerioni
Liana
L
Guidarelli
Andrea
A
Cantoni
Orazio
O
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D020298:U937 Cells
D002070:Butadienes; D003470:Culture Media; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D009570:Nitriles; C113580:U 0126; C015482:protein kinase modulator; D030421:Peroxynitrous Acid; D016718:Arachidonic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one