상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Suppression of RelA/p65 transactivation activity by a lignoid manassantin isolated from Saururus chinensis

Authors 

Jeong-Hyung LeeB Y HwangKyung Sook KimJeong Beom NamYoung-Soo HongJung Joon Lee

Publisher 

Elsevier

Issue Date 

2003

Citation 

Biochemical Pharmacology, vol. 66, no. 10, pp. 1925-1933

Keywords 

apoptosislignoidsNF-κBRelA/p65saururus chinensistransactivationDNAI kappa B alphaimmunoglobulin enhancer binding proteinlipopolysaccharide

Abstract 

In our search for NF-κB inhibitors from natural resources, we have previously identified two structurally related dilignans, manassantin A and B as specific inhibitors of NF-κB activation from Saururus chinensis. However, their molecular mechanism of action remains unclear. We here demonstrate that manassantins A and B are potent inhibitors of NF-κB activation by the suppression of transciptional activity of RelA/p65 subunit of NF-κB. These compounds significantly inhibited the induced expression of NF-κB reporter gene by LPS or TNF-α in a dose-dependent manner. However, these compounds did not prevent the DNA-binding activity of NF-κB assessed by electrophoretic mobility shift assay as well as the induced-degradation of IκB-α protein by LPS or TNF-α. Further analysis revealed that manassantins A and B dose-dependently suppressed not only the induced NF-κB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Furthermore, treatment of cells with these compounds prevented the TNF-α-induced expression of anti-apoptotic NF-κB target genes Bfl-1/A1, a prosurvival Bcl-2 homologue, and resulted in sensitizing HT-1080 cells to TNF-α-induced cell death. Similarly, these compounds also suppressed the LPS-induced inducible nitric oxide synthase expression and nitric oxide production. Taken together, manassantins A and B could be valuable candidate for the intervention of NF-κB-dependent pathological condition such as inflammation and cancer.

ISSN 

0006-2952

Link 

http://dx.doi.org/10.1016/S0006-2952(03)00553-7

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)