DSCR1(Adapt78) modulates expression of SOD1.
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.
Ermak
Gennady
G
Ethel Percy Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
Cheadle
Chris
C
Becker
Kevin G
KG
Harris
Cathryn D
CD
Davies
Kelvin J A
KJ
D000818:Animals; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004790:Enzyme Induction; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1