ERK1/2-dependent regulation of U937 cell survival after exposure to peroxynitrite |
| |
Authors: | Tommasini Ilaria Cerioni Liana Guidarelli Andrea Cantoni Orazio |
| |
Institution: | Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo," Via S. Chiara, 27-61029 Urbino (PU), Italy. |
| |
Abstract: | 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. |
| |
Keywords: | Peroxynitrite Extracellular signal-regulated kinases 1 and 2 Arachidonic acid Cytosolic phospholipase A2 Mitochondrial permeability transition Necrosis |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|