Original contributionH2O2-induced egr-1, fra-1, and c-jun gene expression is mediated by tyrosine kinase in aortic smooth muscle cells
Review articleOpen access
Najia Jin - No affiliation found
2000/10/15 Full-length article DOI: 10.1016/S0891-5849(00)00376-2
Journal: Free Radical Biology and Medicine
AbstractHydrogen peroxide (H2O2) has recently been shown to have a dual effect on cell growth by stimulating proliferation and triggering apoptosis. Apoptosis induced by H2O2 is a direct consequence of oxidant injury, while the proliferative response to H2O2 is thought to be a protective mechanism against oxidant injury. Signaling of the H2O2-induced proliferative effect has been proposed to occur via the activation of mitogen-activated protein kinase (MAPK) and increase in expression of transcription factors. In the present study, H2O2-induced mitogenic signaling in aortic smooth muscle cells (ASMC) was investigated with a specific focus on the roles of tyrosine kinase and tyrosine phosphatase in the regulation of the H2O2-stimulated egr-1, fra-1, and c-jun transcription. The results show that H2O2-induced increases in egr-1, fra-1, and c-jun mRNA levels, as measured by Northern blot analysis, are time and dose dependent with the peak of the response within 2 h. Tyrosine kinase inhibitors (genistein, amino-genistein, and tyrphostin 51) significantly attenuated H2O2-induced expression of these genes and a tyrosine phosphatase inhibitor (perox-vanadate) stimulated their expression. H2O2 stimulated tyrosine kinase activities and caused protein tyrosine phosphorylation, which was blocked by tyrphostin 51. H2O2 also caused tyrosine phosphorylation of platelet derived growth factor (PDGF) receptor. These data show that H2O2 increases egr-1, fra-1, and c-jun mRNA levels in vascular smooth muscle cells, and the increase in expression of these genes is mediated by activation of tyrosine kinase. Our data also provide evidence that the H2O2-induced mitogenic response is, in part, mediated through the receptor tyrosine kinase, PDGF receptor.
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