Cardiac glycosides inhibit TNF-α/NF-κB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor

被引：79

作者：

Yang, QF

Huang, W

Jozwik, C

Lin, Y

Glasman, M

Caohuy, H

Srivastava, M

Esposito, D

Gillette, W

Hartley, J

Pollard, HB

机构：

[1] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA

[2] Uniformed Serv Univ Hlth Sci, Inst Mol Med, Bethesda, MD 20814 USA

[3] NCI, Canc & Cell Biol Branch, NIH, Bethesda, MD 20892 USA

[4] NCI, Prot Express Lab, SAIC, NIH, Frederick, MD 21702 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 27期

关键词：

digitoxin; inflammation;

D O I：

10.1073/pnas.0504097102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-alpha/NF-kappa B signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-alpha-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-kappa B and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event.

引用

页码：9631 / 9636

页数：6

共 37 条

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