The effect of hydrogen peroxide on the cyclin D expression in fibroblasts

Activation of mitogen-activated protein (MAP) kinase is essential for cycli n DI expression and provides a link between mitogenic signalling and cell c ycle progression. Hydrogen peroxide (H2O2) activates MAP kinase; however, i t is not known whether this leads to cyclin D expression. Sustained express ion of cyclin D1 and D2 was observed when Her14 fibroblasts were incubated with 3 mM or higher H2O2 concentrations. Similar results were obtained when cells were incubated in the presence of serum (FCS). However, the sustaine d expression of cyclin D1 and D2 upon H2O2 treatment was not due to the MAP kinase pathway, because MAP kinase kinase inhibitors did not inhibit cycli n D expression. Furthermore, cyclin D1 and D2 levels remained constant even after addition of a protein synthesis inhibitor, indicating that the effec t of H2O2 was not due to induction of protein synthesis. These results indi cate that H2O2 reversibly inhibits the ubiquitin-proteasome dependent degra dation of cyclin D1 and D2, probably by transiently inhibiting ubiquitinati on and/or the proteasome.