Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis

P Angkeow; S S Deshpande; B Qi; Y-X Liu; Y C Park; B H Jeon; M Ozaki; K Irani

doi:10.1038/sj.cdd.4401025

Back

Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis

Journal article

Open access

Peer reviewed

Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis

P Angkeow, S S Deshpande, B Qi, Y-X Liu, Y C Park, B H Jeon, M Ozaki and K Irani

Cell death and differentiation, Vol.9(7), pp.717-725

07/2002

DOI: 10.1038/sj.cdd.4401025

PMID: 12058277

Files and links (1)

url

https://doi.org/10.1038/sj.cdd.4401025View

Published (Version of record) Open Access

Abstract

The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We examined the role of ref-1 in vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1 translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced oxidative stress (H(2)O(2) production), NF-kappaB activation, and apoptosis, and also mitigated rac1-regulated H(2)O(2) production and NF-kappaB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Gene Expression

Oxidative Stress

Apoptosis

Endothelium, Vascular - cytology

Cell Line

Adenoviridae

Carbon-Oxygen Lyases - biosynthesis

Humans

Cytoplasm - metabolism

NF-kappa B - metabolism

Cell Hypoxia

Tumor Necrosis Factor-alpha - pharmacology

Cell Nucleus - metabolism

DNA-(Apurinic or Apyrimidinic Site) Lyase

Carbon-Oxygen Lyases - genetics

Carbon-Oxygen Lyases - metabolism

Genetic Vectors

Details

Title: Subtitle: Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis
Creators: P Angkeow - Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
S S Deshpande
B Qi
Y-X Liu
Y C Park
B H Jeon
M Ozaki
K Irani
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.9(7), pp.717-725
Publisher: England
DOI: 10.1038/sj.cdd.4401025
PMID: 12058277
ISSN: 1350-9047
eISSN: 1476-5403
Grant note: P01 HL65608 / NHLBI NIH HHS
Language: English
Date published: 07/2002
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047769202771

Metrics

15 Record Views

119 Times Cited - Web of Science