This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, H. J.
Right arrow Articles by Kregel, K. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, H. J.
Right arrow Articles by Kregel, K. C.

 Previous Article  |  Next Article 

Journal of Virology, January 2002, p. 355-363, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.355-363.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Redox Regulation of Adenovirus-Induced AP-1 Activation by Overexpression of Manganese-Containing Superoxide Dismutase

Hannah J. Zhang,1 Victoria J. Drake,1 Linjing Xu,1 Jianfang Hu,2 Frederick E. Domann,2 Larry W. Oberley,2 and Kevin C. Kregel1*

Department of Exercise Science, Free Radical and Radiation Biology Program,1 Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa 522422

Received 9 August 2001/ Accepted 20 September 2001

Adenovirus gene therapy is a promising tool in the clinical treatment of many genetic and acquired diseases. However, it has also caused pathogenic effects in organs such as the liver. The redox-sensitive transcription factors AP-1 and NF-{kappa}B have been implicated in these effects. To study the mechanisms of adenovirus-mediated AP-1 and NF-{kappa}B activation and the possible involvement of oxidative stress in adenovirus transduction, rats were injected with either replication-defective recombinant adenovirus with DNA containing the cytomegalovirus promoter region only (AdCMV), adenovirus containing human manganese-containing superoxide dismutase (MnSOD) cDNA (AdMnSOD), or vehicle. Compared to vehicle and AdCMV transduction, MnSOD gene transfer yielded a fivefold increase in liver MnSOD activity 7 days postinjection. Gel shift assay showed that AdCMV transduction induced DNA binding activity for AP-1 but not NF-{kappa}B. MnSOD overexpression abolished this activation. Western blotting analysis of c-Fos and c-Jun suggested that up-regulation of c-fos and c-jun gene expression does not directly contribute to the induction of AP-1 activation. Glutathione/glutathione disulfide ratios were decreased by adenovirus transduction and restored by MnSOD overexpression. The AP-1 binding activity that was induced by AdCMV was decreased by immunoprecipitation of Ref-1 protein. Ref-1 involvement was confirmed by restoration of AP-1 binding activity after the immunoprecipitated Ref-1 protein had been added back. AP-1 DNA binding activity was also elevated in control and AdMnSOD-injected rats after addition of the immunoprecipitated Ref-1 protein. These data indicate that cellular transduction by recombinant adenovirus stimulates AP-1 DNA binding activity. Furthermore, our results suggest that MnSOD overexpression decreases AP-1 DNA binding activity by regulating intracellular redox status, with the possible involvement of Ref-1 in this redox-sensitive pathway.

* Corresponding author. Mailing address: Integrative Physiology Laboratory, 532 FH, The University of Iowa, Iowa City, IA 52242. Phone: (319) 335-7596. Fax: (319) 335-6966. E-mail: kevin-kregel{at}uiowa.edu.

Journal of Virology, January 2002, p. 355-363, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.355-363.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Murthy, S., Adamcakova-Dodd, A., Perry, S. S., Tephly, L. A., Keller, R. M., Metwali, N., Meyerholz, D. K., Wang, Y., Glogauer, M., Thorne, P. S., Carter, A. B. (2009). Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L846-L855 [Abstract] [Full Text]  
  • Kregel, K. C., Zhang, H. J. (2007). An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R18-R36 [Abstract] [Full Text]  
  • Zhang, H. J., Doctrow, S. R., Oberley, L. W., Kregel, K. C. (2006). Chronic antioxidant enzyme mimetic treatment differentially modulates hyperthermia-induced liver HSP70 expression with aging. J. Appl. Physiol. 100: 1385-1391 [Abstract] [Full Text]  
  • O'Malley, Y. Q., Reszka, K. J., Rasmussen, G. T., Abdalla, M. Y., Denning, G. M., Britigan, B. E. (2003). The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L1077-L1086 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»