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DSCR1(Adapl78) modulates expression of SOD1
Author(s) -
Ermak Gennady,
Cheadle Chris,
Becker Kevin G.,
Harris Cathryn D.,
Davies Kelvin J. A.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0451com
Subject(s) - sod1 , oxidative stress , superoxide dismutase , gene expression , microarray analysis techniques , gene , chemistry , microbiology and biotechnology , biology , immunology , endocrinology , genetics
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.— FASEB J. 18, 62–69 (2004)