Inhibitory effect of tyrphostin 47 on Shiga toxin-induced cell death.
The inhibitory effects of tyrosine kinase inhibitors including tyrphostins 25, 47 and 51 on Shiga toxin 1-induced cell death and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were examined in Vero cells. Tyrphostin 47 significantly inhibited Shiga toxin 1-induced cell death and p38 MAPK phosphorylation. In contrast, tyrphostins 25 and 51 had no significant effect on the Shiga toxin 1-induced responses. These data indicate that Shiga toxin 1-induced cell injury occurs through a pathway sensitive to tyrphostin 47, and the target molecule for tyrphostin 47 opens up new opportunities for pharmacological intervention against Shiga toxin-producing Escherichia coli infectious diseases.
Ikeda
Masahiro
M
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Gakuenkibanadai-nishi 1-1, Miyazaki 889-2192, Japan. a0d302u@cc.miyazaki-u.ac.jp
Gunji
Yasuhiro
Y
Sonoda
Hiroko
H
Oshikawa
Sayaka
S
Shimono
Mariko
M
Horie
Atsuko
A
Ito
Katsuaki
K
Yamasaki
Shinji
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002522:Chlorocebus aethiops; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D022621:Shiga Toxin / Q000633:toxicity*; D020032:Tyrphostins / Q000494:pharmacology*; D014709:Vero Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D020032:Tyrphostins; C118515:tyrphostin 51; C079836:tyrphostin 25; C060152:tyrphostin 47; D022621:Shiga Toxin; D048051:p38 Mitogen-Activated Protein Kinases