Journal
ONCOTARGET
Volume 8, Issue 61, Pages 102801-102819Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18462
Keywords
prostaglandin I-2; prostaglandin E-2; tumour necrosis factor alpha; beta-amyloid protein; p38; Gerotarget
Categories
Funding
- National Natural Science Foundation of China [31571064, 81500934, 31300777, 31371091]
- Fundamental Research Funds of China [N152004004, N142004002, N120520001, N120320001, N130120002, N141008001/7, L1520001]
- National Natural Science Foundation of Liaoning, China [2015020662]
- Liaoning Provincial Talent Support Program [LJQ2013029]
Ask authors/readers for more resources
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 A beta(1-42) oligomers but also A beta(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 (A beta)(1-42) in beta-amyloid plaques (APs), which contribute to the cognitive decline of AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available