Differential alterations in antioxidant capacity in cells from Alzheimer patients.
Oxidative stress occurs in brains of Alzheimer's disease (AD) patients. A major question in AD research is whether the oxidative stress is just secondary to neurodegeneration. To test whether oxidative stress is an inherent property of AD tissues, the ability of cultured fibroblasts bearing the AD Presenilin-1 246 Ala-->Glu mutation to handle reactive oxygen species (ROS) was compared to controls. Although ROS in cells from AD subjects were only slightly less than cells from controls under basal conditions (-10%) or after exposure to H(2)O(2) (-16%), treatment with antioxidants revealed clear differences. Pretreatment with DMSO, a hydroxyl radical scavenger, reduced basal and H(2)O(2)-induced ROS levels significantly more in cells from controls (-22%, -22%) than in those from AD subjects (-4%, +14%). On the other hand, pretreatment with Trolox diminished H(2)O(2)-induced ROS significantly more in cells from AD (-60%) than control subjects (-39%). In summary, cells from AD patients have greater Trolox sensitive ROS and less DMSO sensitive ROS than controls. The results demonstrate that fibroblasts bearing this PS-1 mutation have altered means of handling oxidative stress and appear useful for determining the mechanism underlying the altered redox metabolism.
Gibson
G E
GE
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA. ggibson@med.cornell.edu
Zhang
H
H
Sheu
K R
KR
Park
L C
LC
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide; D006863:Hydrogen-Ion Concentration; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D053764:Presenilin-1; D017382:Reactive Oxygen Species / Q000378:metabolism
C096548:6-carboxy-2',7'-dichlorodihydrofluorescein diacetate bis(acetoxymethyl) ester; D000975:Antioxidants; D002839:Chromans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004121:Dimethyl Sulfoxide