title: Mechanism of hydrogen peroxide-induced keratinocyte migration in a scratch-wound model.
abstract: Recent studies have shown that low concentrations of H(2)O(2) are produced endogenously by nonphagocytes after wounding. We observed that H(2)O(2) at such concentrations can stimulate proliferation as well as migration of keratinocytes in a scratch-wound assay. Both wounding and H(2)O(2) can induce phosphorylation of ERK1/2 via EGFR, but the activation of ERK1/2 by H(2)O(2) is more sustained and can last more than 8h. Sustained ERK1/2 activation is required for the increased proliferation and migration induced by H(2)O(2). The p38 MAPK was also found to be phosphorylated upon treatment with H(2)O(2) but it was not required for H(2)O(2)-induced migration or proliferation. Furthermore, it was observed that there is a cross talk between the ERK1/2 and the p38 pathways whereby inhibition of either pathway can lead to activation of the other. As a result, the motogenic effects of H(2)O(2) were further enhanced when p38 was inhibited. Our data are consistent with the view that H(2)O(2) may play an important signaling role in wound healing.
authors.affiliation: Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 119077.
authors.forename: Alvin Eng Kiat
authors.initials: AE
authors.lastname: Loo
authors.forename: Rongjian
authors.initials: R
authors.lastname: Ho
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007093:Imidazoles; D011725:Pyridines; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580