DSCR1(Adapt78) modulates expression of SOD1

Gennady Ermak, Chris Cheadle, Kevin G. Becker, Cathryn D. Harris, Kelvin J.A. Davies

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)62-69
Number of pages8
JournalFASEB Journal
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2004

Keywords

  • Calcipressin 1
  • Down's syndrome
  • Oxidative stress
  • Sod 1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Ermak, G., Cheadle, C., Becker, K. G., Harris, C. D., & Davies, K. J. A. (2004). DSCR1(Adapt78) modulates expression of SOD1. FASEB Journal, 18(1), 62-69. https://doi.org/10.1096/fj.03-0451com