The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress.
Although DSCR1 (Adapt78) has been associated with successful adaptation to oxidative stress and calcium stress and with devastating diseases such as Alzheimer's and Down syndrome, no rationale for these apparently contradictory findings has been tested. In fact, DSCR1 (Adapt78) has not yet been proved to provide protection against acute oxidative stress or calcium stress. We have addressed this question using cross-adaptation to H2O2 and the calcium ionophore A23187, stable DSCR1 (Adapt78) transfection and overexpression in hamster HA-1 cells, 'tet-off' regulated DSCR1 (Adapt78) isoform 1 transgene expression in human PC-12 cells, and DSCR1 (Adapt78) antisense oligonucleotides to test the ability of the DSCR1 (Adapt78) protein product calcipressin 1 (a calcineurin inhibitor) to protect against oxidative stress and calcium stress. Under all conditions, resistance to oxidative stress and calcium stress increased as a function of DSCR1 (Adapt78)/calcipressin 1 expression and decreased as gene/protein expression diminished. We conclude that cells may transiently use increased expression of the DSCR1 (Adapt78) gene product calcipressin 1 to provide short-term protection against acute oxidative stress and other calcium-mediated stresses, whereas chronic overexpression may be associated with Alzheimer disease progression.
Ermak
Gennady
G
Ethel Percy Andrus Gerontology Center, and Division of Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089-0191, USA.
Harris
Cathryn D
CD
Davies
Kelvin J A
KJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D016373:DNA, Antisense / Q000494:pharmacology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007476:Ionophores / Q000494:pharmacology; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014162:Transfection
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007476:Ionophores; D009124:Muscle Proteins; D016877:Oxidants; C108612:RCAN1 protein, human; D012333:RNA, Messenger; D000001:Calcimycin; D006861:Hydrogen Peroxide; D019703:Calcineurin; D002118:Calcium