The phosphorylation state of MAP-kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide.
Micromolar concentrations of hydrogen peroxide induced the phosphorylation of mitogen-activated protein (MAP) kinases and a lethal response in growth-arrested smooth muscle cells (A7r5). The H202-induced phosphorylation of MAP-kinases was markedly lower in the presence of protein tyrosine kinase (PTK) inhibitors or in protein kinase C (PKC) down-regulated cells. Similarly, the toxicity of H202 was diminished by concomitant addition of either PKC or PTK inhibitors and was also lower in PKC down-regulated cells. These results are consistent with the possibility that phosphorylation of MAP-kinases is a critical event in the toxic response of cultured smooth muscle cells to H202.
Cantoni
O
O
Istituto di Chimica Biologica, Università degli Studi di Urbino, Italy.
Boscoboinik
D
D
Fiorani
M
M
Stäuble
B
B
Azzi
A
A
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D020032:Tyrphostins
D002396:Catechols; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009570:Nitriles; D020032:Tyrphostins; C061465:calphostin complex; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C060641:tyrphostin A23