| First Author | Zheng SQ | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 61 | Pages | 102801-102819 |
| PubMed ID | 29262525 | Mgi Jnum | J:368393 |
| Mgi Id | MGI:8215221 | Doi | 10.18632/oncotarget.18462 |
| Citation | Zheng SQ, et al. (2017) Prostaglandin I(2) is responsible for ameliorating prostaglandin E(2) stress in stimulating the expression of tumor necrosis factor alpha in a beta-amyloid protein -dependent mechanism. Oncotarget 8(61):102801-102819 |
| abstractText | Cyclooxygenase-2 (COX-2) has been found to be induced during the early stage of Alzheimer's disease (AD). Using mouse-derived astrocyte and APP/PS1 transgenic (Tg) mice as model systems, we firstly elucidated the mechanisms underlying COX-2 metabolic production including prostaglandin (PG)E(2)- and PGI(2)-mediated tumor necrosis factor alpha (TNF-alpha) regulation. Specifically, PGE(2) accumulation in astrocyte activated the p38 and JNK/c-Jun signaling pathways via phosphorylation, resulting in TNF-alpha expression. In contrast, the administration of PGI(2) attenuated the effects of PGE(2) in stimulating the production of TNF-alpha by inhibiting the activity of TNF-alpha promoter and the binding activity of AP1 on the promoter of TNF-alpha. Moreover, our data also showed that not only Abeta(1-42) oligomers but also Abeta(1-42) fibrils have the ability to involve in mediating the antagonistic effects of PGE(2) and PGI(2) on regulating the expression of TNF-alpha via a p38- and JNK/c-Jun-dependent, AP1-transactivating mechanism. Reciprocally, the production of TNF-alpha finally accelerated the deposition of beta-amyloid protein (Abeta)(1-42) in beta-amyloid plaques (APs), which contribute to the cognitive decline of AD. |
