Mitochondrial H2O2 limits U937 cell survival to peroxynitrite by promoting ERK1/2 dephosphorylation

We report that the inhibitory effects of H2O2 are at the level of extracellular signal-regulated kinase 1 and 2 phosphorylation and involve activation of orthovanadate-sensitive phosphotyrosine protein phosphatase(s)

Liana Cerioni

2007

Scholarcy highlights

  • Sequential activation of cytosolic phospholipase A2 and 5-lipoxygenase, critically regulated by extracellular signal-regulated kinase 1 and 2-dependent phosphorylation, mediates U937 cell survival to peroxynitrite
  • A limiting factor is represented by the parallel mitochondrial formation of H2O2 leading to suppression of the survival signaling
  • We report that the inhibitory effects of H2O2 are at the level of ERK1/2 phosphorylation and involve activation of orthovanadate-sensitive phosphotyrosine protein phosphatase(s)
  • The otherwise stimulatory effects of peroxynitrite on ERK1/2 phosphorylation are concealed by phosphatase-dependent dephosphorylation and the activities of cytosolic phospholipase A2 and 5-LO are significantly reduced or suppressed, respectively
  • The ensuing inhibition of downstream events preventing mitochondrial permeability transition rapidly leads these cells to death
  • Endogenous H2O2 limits U937 cell survival to peroxynitrite via activation of phosphotyrosine protein phosphatase(s) promoting upstream inhibition of the survival signaling critically regulated by the extent of ERK1/2 phosphorylation

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