Tripterine prevents endothelial barrier dysfunction by inhibiting peroxynitrite synthesis
Wu, F; Wilson, JX
HERO ID
976555
Reference Type
Journal Article
Subtype
Abstract
Year
2008
Language
English
| HERO ID | 976555 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2008 |
| Title | Tripterine prevents endothelial barrier dysfunction by inhibiting peroxynitrite synthesis |
| Authors | Wu, F; Wilson, JX |
| Journal | Free Radical Biology and Medicine |
| Volume | 45 |
| Issue | Suppl. |
| Page Numbers | S93-S93 |
| Abstract | Tripterine is an active component of Tripterygium wilfordii Hook F., which is used in traditional Chinese medicine to treat inflammatory diseases such as rheumatoid arthritis. a hallmark of inflammation is increased microvascular permeability due to endothelial barrier dysfunction. We hypothesized that tripterine prevents the endothelial barrier dysfunction triggered by the inflammatory insult of lipopolysaccharide (LPS) and interferon γ (IFNγ). Εxposure of mouse microvascular endothelial cell monolayers to LPS+IFNγ increased the permeability to albumin, the expression of iNOS and NADPH oxidase type 1 (Nox1) proteins, and the production of nitric oxide (NO), superoxide and peroxynitrite. Tripterine inhibited these responses to LPS+IFNγ significantly. the induction of iNOS and Nox1 by LPS+IFNγ was also attenuated by the NFκB inhibitor MG132, the MEK1/2 inhibitor PD98059, the JNK inhibitor SP600125 and the Jak2 inhibitor AG490, but not by the p38 MAPK inhibitor SB203580. LPS+IFNγ stimulated the degradation of IκB and phosphorylation of ERK, JNK and Jak2, but only the phosphorylation of Jak2 was sensitive to tripterine. We conclude that, in microvascular endothelial cells exposed to LPS+IFNγ, iNOS-derived NO and NADPH oxidase-derived superoxide react to form peroxynitrite that causes barrier dysfunction. by inhibiting Jak2-dependent induction of iNOS and Nox1, tripterine prevents synthesis of peroxynitrite and consequently preserves the endothelial barrier. |
| Wosid | WOS:000260867900266 |
| Url | http://www.sciencedirect.com/science/article/pii/S0891584908006254 |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Indianapolis, IN |
| Conference Name | Society for Free Radical Biology and Medicine15th Annual Meeting |
| Conference Date | November 19-23, 2008 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
|