NT2 neurons, a classical model for Alzheimer's disease, are highly susceptible to oxidative stress.
We have tested undifferentiated NT2 cells as well as differentiated NT2 neurons (NT2N) for vulnerability to oxidative stress, lipid composition and antioxidant pattern. NT2N, but not NT2 cells, are highly susceptible to oxidative stress elicited by different classic pro-oxidant stimuli. In particular, NT2N cells undergo a high level of oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) of membrane phospholipids, as evaluated by monitoring generation of thiobarbituric reactive substances, 4-hydroxynonenal (HNE) and chromolipid fluorescent adducts. NT2N cells exhibit low levels of natural antioxidants such as glutathione (GSH) and alpha-tocopherol and of antioxidant enzymatic activities such as Se-dependent GSH peroxidase and catalase. Accordingly, a direct correlation between lipid peroxidation and irreversible cell damage is suggested by prevention of NT2N cell death by alpha-tocopherol.
Tamagno
E
E
Department of Experimental Medicine and Oncology, University of Turin, Italy.
Aragno
M
M
Parola
M
M
Parola
S
S
Brignardello
E
E
Boccuzzi
G
G
Danni
O
O
D000544:Alzheimer Disease / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D016923:Cell Death; D002454:Cell Differentiation; D004338:Drug Combinations; D005227:Fatty Acids / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology
D004338:Drug Combinations; D005227:Fatty Acids; D005296:Ferrous Compounds; D008054:Lipid Peroxides; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C020748:ferrous sulfate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D001205:Ascorbic Acid