Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase

Michitaka Ozaki; Seiichi Suzuki; Kaikobad Irani

doi:10.1096/fj.01-0664fje

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Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase

Journal article

Peer reviewed

Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase

Michitaka Ozaki, Seiichi Suzuki and Kaikobad Irani

The FASEB journal, Vol.16(8), pp.889-890

06/2002

DOI: 10.1096/fj.01-0664fje

PMID: 12039869

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Abstract

Oxidative stress triggered by many environmental and clinical insults results in cellular injury and death. The small GTPase rac1 promotes oxidative stress via the production of reactive oxygen species (ROS). In turn, the homeostatic response to such stress includes up-regulation of the dual function reducing protein/DNA repair enzyme APE/redox factor-1(ref-1). In this report we explore the function and relationship between ref-1 and rac1 in the setting of oxidative stress triggered by re-oxygenation/reperfusion. In a model of mouse hepatic ischemia/reperfusion (I/R), recombinant adenoviral overexpression of ref-1 resulted in suppression of reperfusion-stimulated oxidative stress, NF-kB induction, apoptosis, and acute injury, whereas down-regulation of endogenous ref-1 by adenoviral expression of antisense ref-1 led to an increase in these reperfusion-induced parameters. Ref-1 also mitigated ROS production induced by adenoviral expression of an active form of rac1. Finally, overexpression of ref-1 in primary hepatocytes suppressed reoxygenation-stimulated rac1 activity. This work demonstrates a novel function of ref-1 in inhibition of rac1 activity, and rac1-mediated oxidative stress and injury.

Oxygen - pharmacology

Liver - pathology

Reactive Oxygen Species - metabolism

Liver - metabolism

Oxidative Stress - physiology

NF-kappa B - metabolism

Animals

DNA-(Apurinic or Apyrimidinic Site) Lyase

Reperfusion

Liver - drug effects

Carbon-Oxygen Lyases - genetics

Superoxides - metabolism

Mice

Carbon-Oxygen Lyases - physiology

rac1 GTP-Binding Protein - metabolism

Details

Title: Subtitle: Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase
Creators: Michitaka Ozaki - Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Seiichi Suzuki
Kaikobad Irani
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.16(8), pp.889-890
DOI: 10.1096/fj.01-0664fje
PMID: 12039869
NLM abbreviation: FASEB J
eISSN: 1530-6860
Publisher: United States
Grant note: DOI: 10.13039/100000968, name: American Heart Association; DOI: 10.13039/100001340, name: W. W. Smith Charitable Trust; DOI: 10.13039/100000002, name: National Institutes of Health, award: P01 HL65608
Language: English
Date published: 06/2002
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984046807702771

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