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.