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* Department of Medicine, University of California, Irvine, Orange, California 92868; and
World Health Organization Collaborating Center for Virus Reference and Research, Laboratory of Virology, 69373 Lyon cedex 08, France
To whom requests for reprints should be addressed at 1 UCI Medical Center, Department of Medicine/Infectious Diseases, 101 City Drive South, Building 11, Orange, CA 92868. E-mail: mberger{at}uci.edu or matschiberger{at}yahoo.com
The relationship between oxidative stress and neuronal cell death has been suggested for many years. To understand the influence of oxidative stress on neuronal cell death, we investigated the influence of oxidative stress on DEV cells, a human glial cell line. Using enterovirus infection and/or malnutrition to induce oxidative stress, our results demonstrate that those stressors severely influence the antioxidant defense system in DEV cells. Although the expression of mitochondrial manganese superoxide dismutase (MnSOD) in DEV cells was significantly increased in acute infection with viral and nutritional stress, in persistent infection and nutritional stress, the expression of the MnSOD was drastically downregulated. We believe that this downregulation of MnSOD expression in the chronic stress model is due to repression of antioxidant defense. The downregulation of the MnSOD expression may lead to an increase of free-radical production and thus explain why the cells in the chronic stress model were more vulnerable to other oxidative stress influences. The vulnerability of DEV cells to additional stress factors resulted in progressive cell death, which may be analogous to the cell death in neurodegenerative diseases.
Key Words: in vitro stress model oxidative stress persistent virus infection enteroviruses
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