Enhanced ROS-generation in lymphocytes from Alzheimer's patients.
BACKGROUND
Reactive oxygen species (ROS) have been implicated in neurodegeneration and seem to be involved in the physiology and pathophysiology of several diseases, including normal aging and Alzheimer's disease (AD). Enhanced ROS production in aging or AD is not restricted to the brain, but can also been seen in several peripheral tissues. The objective of the present study was to evaluate whether the mechanisms involved in the generation of oxidative stress in normal senescence and Alzheimer's disease are identical or not.


METHODS
We analysed intracellular basal levels of ROS in lymphocytes from AD patients and healthy young and aged not-demented subjects as well as ROS levels following stimulation with d-ribose and staurosporine in all three groups. ROS levels were measured by flow cytometry using the intracellular fluorescence dye dihydrorhodamine123 (DHR123).


RESULTS
Our study shows that AD lymphocytes have increased basal levels of ROS, low susceptibility to ROS stimulation by 2-deoxy- D-ribose (dRib) and an increased response to staurosporine when compared with age-matched controls.


CONCLUSIONS
The data suggest that the defect(s) responsible for enhanced ROS production in AD may involve different or additional biological pathways than those involved in enhanced ROS generation during aging.
Leutner
S
S
Department of Pharmacology, Biocenter, J. W. Goethe University of Frankfurt, Marie-Curie-Str. 9, 60439 Frankfurt am Main, Germany.
Schindowski
K
K
Frölich
L
L
Maurer
K
K
Kratzsch
T
T
Eckert
A
A
Müller
W E
WE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D003855:Deoxyribose / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012235:Rhodamines; D019311:Staurosporine / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D012235:Rhodamines; C058319:dihydrorhodamine 123; D003855:Deoxyribose; D019311:Staurosporine