These results, together with the increased accumulation of c-H2AX foci at sites of newly replicated DNA, indicate the presence of replication stress. Thus, WRN is required to minimize replication-associated damage in response to c-Myc driven S-phase. p53 is required for the intra-S checkpoint activated by low doses of radiation. This is consistent with our findings of increased phosphorylation of p53. Collectively, there appears a solid foundation to expect a beneficial effect from antioxidant treatment. The absence of protection suggests that nonspecific antioxidants are insufficient to AG-013736 inquirer eliminate untoward reactive oxygen species in exercising muscle. Mitochondria are the predominant contributor of cellular reactive oxygen species. Manganese superoxide dismutase and glutathione peroxidase constitute the primary antioxidant defense system in the mitochondria. Because members of the NF-kB pathway are increasingly recognized as important in the regulation of epithelial-mesenchymal interaction systems, ranging from tooth development to hair follicle induction and morphogenesis, we were interested in learning whether TAK1 also played a role in the biology of the hair follicle, a prototypic epithelial-mesenchymal
interaction system. This interest was further fueled by our previous discovery in keratinocyte-specific TAK1-deficient mice that TAK1 regulates keratinocyte growth, differentiation, and apoptosis. However, the role of TAK1 in hair follicles has not been previously studied. Induction and morphogenesis of the hair follicle is controlled by complex signaling networks within the skin epithelium and between the epithelium and specialized inductive fibroblasts in its adjacent mesenchyme. Among these signaling networks, the NF-kB pathway and Wnt/b-catenin signaling provide central controls ; however, the exact relationship between these signaling networks is not fully understood. Binding of EdaA1 to its receptor EdaR in the embryo is essential for the development of ectodermal appendages, and mutations in these genes cause reduced or absent ectodermal appendages. Subsequently, the EdaA1/EdaR pathway activates the downstream NF-kB pathway. Briefly, MnSOD converts superoxide radicals to hydrogen peroxide. Hydrogen peroxide is then reduced by GPX into water. When hydrogen peroxide is not completely detoxified, it readily forms highly reactive and cytotoxic hydroxyl radicals. Our study was performed using primary human monocytes in which productive EBV infection and viral-mediated alteration of several cellular functions have been demonstrated. Here, we have shown that EBV infection induces SOCS3 activation via Zta and alters the IFNa signaling pathway. Using such a strategy, EBV might be able to survive longer within monocytes and optimize its dissemination.