| First Author | Almeida M | Year | 2010 |
| Journal | Mol Endocrinol | Volume | 24 |
| Issue | 10 | Pages | 2030-7 |
| PubMed ID | 20685851 | Mgi Jnum | J:182837 |
| Mgi Id | MGI:5316948 | Doi | 10.1210/me.2010-0189 |
| Citation | Almeida M, et al. (2010) Oxidative stress stimulates apoptosis and activates NF-kappaB in osteoblastic cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol Endocrinol 24(10):2030-7 |
| abstractText | Aging or acute loss of estrogens or androgens increases the levels of reactive oxygen species, activates nuclear factor-kappaB (NF-kappaB), and promotes the phosphorylation of p66(shc), a redox enzyme that amplifies mitochondrial reactive oxygen species generation and stimulates apoptosis. We report that in mesenchymal progenitor and osteoblastic cell models, H(2)O(2) activated a protein kinase C (PKC)beta/p66(shc)/NF-kappaB signaling cascade and that p66(shc) was an essential mediator of the stimulating effects of H(2)O(2) on the apoptosis of osteoblastic cells as well as their ability to activate NF-kappaB. 17beta-Estradiol (E(2)) or the nonaromatizable androgen dihydrotestosterone abrogated the effects of H(2)O(2) on p66(shc) and NF-kappaB activation by attenuating the phosphorylation of the redox-sensitive cytoplasmic kinase PKCbeta. Additionally, both E(2) and dihydrotestosterone prevented H(2)O(2)-induced apoptosis by a mechanism that involved attenuation of p66(shc) resulting from decreased phosphorylation of PKCbeta. Consistent with a kinase-mediated mechanism of sex steroid action, the effects of E(2) were reproduced by a polymeric form of estradiol that is not capable of stimulating the nuclear-initiated actions of ERalpha. These results demonstrate that p66(shc) is an essential mediator of the effects of oxidative stress on osteoblastic cell apoptosis, NF-kappaB activation, and cytokine production. The ability of either estrogen or androgen to attenuate the effects of oxidative stress on osteoblastic cell apoptosis, NF-kappaB activation, and cytokine production results from their common property to suppress PKCbeta-induced p66(shc) phosphorylation via a mechanism that does not require stimulation of the nuclear-initiated actions of sex steroids. |
