Shiga toxin activates p38 MAP kinase through cellular Ca2+ increase in Vero cells

We examined whether the mitogen-activated protein kinase (MAPK) pathway is involved in Shiga toxin (Stx)-induced Vero cell injury. Consonant,vith cell injury, Stx caused a transient extracellular signal-regulated kinase1/2 (ERK1/2) and a sustained p38 MAPK phosphorylation. p38 MAPK inhibitors (SB 203580 and PD 169316), but not an ERK1/2 kinase inhibitor (PD 98059), partially inhibited the Stx-induced cell death. BAPTA-AM, a Ca2+ chelator, reduced both cell injury and p38, MAPK phosphorylation. Antioxidants reduced Stx1-induced p38 MAPK phosphorylation. These data indicate that Stx activates p38 MAPK through an increase in intracellular Ca2+ and reactive oxygen species, and this signaling is involved in Stx-induced fell death. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.