eCite Digital Repository
A novel form of ataxia oculomotor apraxia characterized by oxidative stress and apoptosis resistance
Citation
Gueven, N and Becherel, OJ and Howe, O and Chen, P and Haince, J-F and Ouellet, M-E and Poirier, GG and Waterhouse, N and Fusser, M and Epe, B and de Murcia, JM and de Murcia, G and McGowan, CH and Parton, R and Mothersill, C and Grattan-Smith, P and Lavin, MF, A novel form of ataxia oculomotor apraxia characterized by oxidative stress and apoptosis resistance, Cell Death and Differentiation, 14, (6) pp. 1149-1161. ISSN 1350-9047 (2007) [Refereed Article]
Copyright Statement
Copyright 2007 Nature Publishing Group
DOI: doi:10.1038/sj.cdd.4402116
Abstract
Several different autosomal recessive genetic disorders characterized by ataxia with oculomotor apraxia (AOA) have been identified with the unifying feature of defective DNA damage recognition and/or repair. We describe here the characterization of a novel form of AOA showing increased sensitivity to agents that cause single-strand breaks (SSBs) in DNA but having no gross defect in the repair of these breaks. Evidence for the presence of residual SSBs in DNA was provided by dramatically increased levels of poly (ADP-ribose)polymerase (PARP-1) auto-poly (ADP-ribosyl)ation, the detection of increased levels of reactive oxygen/nitrogen species (ROS/RNS) and oxidative damage to DNA in the patient cells. There was also evidence for oxidative damage to proteins and lipids. Although these cells were hypersensitive to DNA damaging agents, the mode of death was not by apoptosis. These cells were also resistant to TRAIL-induced death. Consistent with these observations, failure to observe a decrease in mitochondrial membrane potential, reduced cytochrome c release and defective apoptosis-inducing factor translocation to the nucleus was observed. Apoptosis resistance and PARP-1 hyperactivation were overcome by incubating the patient's cells with antioxidants. These results provide evidence for a novel form of AOA characterized by sensitivity to DNA damaging agents, oxidative stress, PARP-1 hyperactivation but resistance to apoptosis.
Item Details
Item Type: | Refereed Article |
---|---|
Keywords: | ataxia oculomotor apraxia, cell death |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Neurology and neuromuscular diseases |
Objective Division: | Health |
Objective Group: | Other health |
Objective Field: | Other health not elsewhere classified |
UTAS Author: | Gueven, N (Dr Nuri Guven) |
ID Code: | 79281 |
Year Published: | 2007 |
Web of Science® Times Cited: | 12 |
Deposited By: | Pharmacy |
Deposited On: | 2012-08-29 |
Last Modified: | 2014-11-04 |
Downloads: | 0 |
Repository Staff Only: item control page