Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-5-22
pubmed:abstractText
The effects of nuclear-localized oxidative stress on both nuclear antioxidant systems, and the processes that they regulate, are not clearly understood. Here, we targeted a hydrogen peroxide (H(2)O(2))-producing enzyme, D-amino acid oxidase (DAAO), to the nucleus (NLS-DAAO) and used this to generate H(2)O(2) in the nuclei of cells. On addition of N-acetyl-D-alanine (NADA), a substrate of DAAO, to NLS-DAAO-transfected HeLa cells, a twofold increase in ROS production relative to untreated, transfected control was observed. Staining of cellular thiols confirmed that NLS-DAAO-induced ROS selectively modified the nuclear thiol pool, whereas the cytoplasmic pool remained unchanged. Furthermore, NLS-DAAO/NADA-induced ROS caused significant oxidation of the nuclear GSH pool, as measured by nuclear protein S-glutathionylation (Pr-SSG), but under the same conditions, nuclear Trx1 redox state was not altered significantly. NF-kappaB reporter activity was diminished by NLS-DAAO/NADA-stimulated nuclear oxidation. We conclude that nuclear GSH is more susceptible to localized oxidation than is nuclear Trx1. Furthermore, the attenuation of NF-kappaB reporter activity in the absence of nuclear Trx1 oxidation suggests that critical nuclear redox proteins are subject to control by S-glutathionylation during oxidative stress in the nucleus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1523-0864
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
807-16
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17508907-Active Transport, Cell Nucleus, pubmed-meshheading:17508907-Alanine, pubmed-meshheading:17508907-Blotting, Western, pubmed-meshheading:17508907-Cell Nucleus, pubmed-meshheading:17508907-Cell Survival, pubmed-meshheading:17508907-D-Amino-Acid Oxidase, pubmed-meshheading:17508907-Glutathione, pubmed-meshheading:17508907-Glutathione Disulfide, pubmed-meshheading:17508907-HeLa Cells, pubmed-meshheading:17508907-Humans, pubmed-meshheading:17508907-Hydrogen Peroxide, pubmed-meshheading:17508907-Immunoprecipitation, pubmed-meshheading:17508907-Models, Biological, pubmed-meshheading:17508907-NF-kappa B, pubmed-meshheading:17508907-Oxidation-Reduction, pubmed-meshheading:17508907-Oxidative Stress, pubmed-meshheading:17508907-Reactive Oxygen Species, pubmed-meshheading:17508907-Thioredoxins, pubmed-meshheading:17508907-Transfection
pubmed:year
2007
pubmed:articleTitle
Selective oxidative stress in cell nuclei by nuclear-targeted D-amino acid oxidase.
pubmed:affiliation
Division of Pulmonary, Allergy, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural