Influence of cell culture conditions on the protective effect of antioxidants against beta-amyloid toxicity: studies with lazaroids.
The mechanisms of cell death of rat cortical neurons chronically exposed to the beta-amyloid (betaA) biologically active fragment beta-(25-35) involve oxidative stress. We examined the influence of culture conditions on the neuroprotective activity of antioxidants against beta-(25-35) toxicity. Common radical scavengers such as N-acetylcysteine (250 microM) and N-t-butyl-phenylnitrone (500 microM) only protected cortical cells cultured in the presence of fetal calf serum (FCS) from betaA insult. The neuroprotective effect of lazaroids (U74389G and U83836E), 21-aminosteroids with antioxidant activity, was tested in cells grown with or without FCS. U74389G did not interfere with beta-(25-35) toxicity in either condition, while U83836E at a very low concentration (15 nM) protected cortical cells exposed to the beta peptide only when the neurons were cultured in the presence of FCS. These data show that a lazaroid can prevent beta-(25-35) toxicity and that the antioxidants exerted their protective effect in certain conditions.
Lucca
E
E
Biology of Neurodegenerative Disorders Laboratory, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Angeretti
N
N
Forloni
G
G
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010879:Piperazines; D011281:Pregnatrienes; C074965:U 74389F; C066382:U 78517F