Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid

Gatei, M, Shkedy, D, Khanna, KK, Uziel, T, Shiloh, Y, Pandita, TK, Lavin, MF and Rotman, G (2001) Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid. Oncogene, 20 3: 289-294. doi:10.1038/sj.onc.1204111


Author Gatei, M
Shkedy, D
Khanna, KK
Uziel, T
Shiloh, Y
Pandita, TK
Lavin, MF
Rotman, G
Title Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1038/sj.onc.1204111
Volume 20
Issue 3
Start page 289
End page 294
Total pages 6
Place of publication UK
Publisher Nature Publishing Group
Collection year 2001
Language eng
Subject C1
270103 Protein Targeting and Signal Transduction
730108 Cancer and related disorders
Abstract Cells from patients with the genetic disorder ataxia-telangiectasia (A-T) are hypersensitive to ionizing radiation and radiomimetic agents, both of which generate reactive oxygen species capable of causing oxidative damage to DNA and other macromolecules. We describe in A-T cells constitutive activation of pathways that normally respond to genotoxic stress, Basal levels of p53 and p21(WAF1/CIP1), phosphorylation on serine 15 of p53, and the Tyr15-phosphorylated form of cdc2 are chronically elevated in these cells. Treatment of A-T cells with the antioxidant alpha -lipoic acid significantly reduced the levels of these proteins, pointing to the involvement of reactive oxygen species in their chronic activation. These findings suggest that the absence of functional ATM results in a mild but continuous state of oxidative stress, which could account for several features of the pleiotropic phenotype of A-T.
Keyword Biochemistry & Molecular Biology
Oncology
Cell Biology
Genetics & Heredity
Ataxia-telangiectasia
Atm
P53
P21(waf1/cip1)
Cdc2
Alpha-lipoic Acid
Oxidative Stress
Double-strand Breaks
Cell-cycle Checkpoints
Atm-deficient Mice
Dna-damage
Oxidative Damage
Induced Phosphorylation
Genotoxic Stress
Gene-product
Repair
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 01:56:34 EST