title: Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis.
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.
authors.affiliation: Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Angkeow
authors.forename: S S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: B
authors.initials: B
authors.lastname: Qi
authors.forename: Y-X
authors.initials: YX
authors.lastname: Liu
authors.forename: Y C
authors.initials: YC
authors.lastname: Park
authors.forename: B H
authors.initials: BH
authors.lastname: Jeon
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: K
authors.initials: K
authors.lastname: Irani
mesh_terms: D000256:Adenoviridae; D017209:Apoptosis; D019757:Carbon-Oxygen Lyases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase