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(The FASEB Journal. 2004;18:62-69.)
© 2004 FASEB

DSCR1(Adapt78) modulates expression of SOD1

GENNADY ERMAK*, CHRIS CHEADLE{dagger}, KEVIN G. BECKER{dagger}, CATHRYN D. HARRIS* and KELVIN J. A. DAVIES*,1

* Ethel Percy Andrus Gerontology Center, and Division of Molecular & Computational Biology, The University of Southern California, Los Angeles, CA 90089-0191, USA; and
{dagger} DNA Array Unit, Research Resources Branch, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore MD 21224-6825, USA

1Correspondence: Ethel Percy Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. E-mail: kelvin{at}usc.edu

DSCR1(Adapt78) is a stress responsive gene that can be induced by multiple stresses. We have previously demonstrated that acute DSCR1(Adapt78) overexpression can transiently protect cells against oxidative stress and calcium-mediated stresses, while its chronic overexpression is associated with neurofibrillary tangles, Alzheimer disease, and Down’s syndrome. It seems that a delicate balance of DSCR1(Adapt78) expression is maintained in cells, and this gene can have either protective or damaging effects, depending on both its level and duration of expression. The mechanisms by which DSCR1(Adapt78) can protect or harm cells are poorly understood. Here, we tried to identify pathways and targets affected by the DSCR1(Adapt78) gene using regulated expression of DSCR1(Adapt78) in PC-12 cells, followed by microarray analysis of mRNAs from these cells. We found that DSCR1(Adapt78) expression stimulates SOD1 (intracellular Cu,Zn superoxide dismutase) gene expression and increased sod 1 enzyme activity. Previous studies have indicated that sod 1 can either protect or damage cells, depending on its levels. Our findings suggest that sod 1 may also be involved in both the acute protective and the chronic damaging effects of DSCR1(Adapt78) expression. These data also have importance for our understanding of Down’s syndrome, Alzheimer’s disease, and other human pathologies.


Key Words: calcipressin 1 • sod 1 • oxidative stress • Down’s syndrome




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