Journal article
Cellular redox state alters recombinant adenoassociated virus transduction through tyrosine phosphatase pathways
Gene therapy, Vol.6(8), pp.1427-1437
1999
DOI: 10.1038/sj.gt.3300967
Abstract
Several types of environmental damage including UV, hydroxyurea and ionizing irradiation have been shown to augment rAAV transduction. Current hypotheses suggest that these environmental stimuli lead to the enhanced production and/or activation of cellular factors important in the conversion of single-stranded DNA genomes to expressible forms. However, the mechanisms of action are currently unknown. We hypothesized that reactive oxygen intermediates (ROl) may play a common role in the augmentation of rAAV transduction by these environmental stimuii. Our results demonstrate that treatment with hydrogen peroxide can give equivalent or greater levels of augmentation in rAAV transduction as that seen by hydroxy-urea or UV irradiation. For all environmental stimuli, pretreatment with the hydroxyl radical (HO) scavenger, N-acetyl-L-cysteine (NAC), completely blocked augmentation of rAAV transduction. Furthermore, using election spin resonance spectroscopy (ESR), we demonstrated that both UV and H2O2 treatment of cell lines lead to the induction of HO radicals. Our results demonstrating that NaOV inhibits the augmentation of rAAV transduction following UV and H2O2 treatment, implicate HO radicals as modulators of tyrosine phosphatase pathways involved in rAAV transduction. Alterations in the cellular redox state and subsequent activation of tyrosine phosphatase pathways appear to alter the phosphorylation status of the previously identified single stranded sequence binding protein (ssD-BP), with reduced phosphorylation correlating with an enhancement in rAAV transduction. In summary, we conclude that the cellular redox state may play an important role in regulating rAAV transduction.
Details
- Title: Subtitle
- Cellular redox state alters recombinant adenoassociated virus transduction through tyrosine phosphatase pathways
- Creators
- S Sanlioglu - University of IowaJ. F Engelhardt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.6(8), pp.1427-1437
- DOI
- 10.1038/sj.gt.3300967
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 1999
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284324202771
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