FERM domain promotes resveratrol-induced apoptosis in endothelial cells via inhibition of NO production
  • Lee, Hye-Rim
  • Kim, Jongmin
  • Park, Jinsun
  • Ahn, Sunyoung
  • Jeong, Eunsil
  • 외 1명
Citations

WEB OF SCIENCE

10
Citations

SCOPUS

9

초록

Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 mu M resveratrol, whereas FERM had no effect on apoptosis induced by TNF-alpha. We determined that resveratrol at low doses (<20 mu M) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production. (C) 2013 Elsevier Inc. All rights reserved.

키워드

FERMFAKApoptosisResveratrolEndothelial cellsFOCAL ADHESION KINASENITRIC-OXIDE PRODUCTIONX-LINKED INHIBITORTYROSINE PHOSPHORYLATIONTERMINAL DOMAINPROTEINEXPRESSIONXIAPLOCALIZATIONCLEAVAGE
제목
FERM domain promotes resveratrol-induced apoptosis in endothelial cells via inhibition of NO production
저자
Lee, Hye-RimKim, JongminPark, JinsunAhn, SunyoungJeong, EunsilPark, Heonyong
DOI
10.1016/j.bbrc.2013.10.154
발행일
2013-11
유형
Article
저널명
Biochemical and Biophysical Research Communications
441
4
페이지
891 ~ 896