Shiga toxin activates p38 MAP kinase through cellular Ca(2+) 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 with 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 Ca(2+) 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 Ca(2+) and reactive oxygen species, and this signaling is involved in Stx-induced cell death.
Ikeda
M
M
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan. a0d302u@cc.miyazaki-u.ac.jp
Gunji
Y
Y
Yamasaki
S
S
Takeda
Y
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002614:Chelating Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D022621:Shiga Toxin / Q000494:pharmacology*; D015398:Signal Transduction; D014709:Vero Cells; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D022621:Shiga Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium