Evaluation of neurotoxicity of alzheimer's amyloid beta protein (beta42) in cultured hippocampal cells and its prevention by propentofylline.
Neurotoxicity of beta42 (20 microM) in cultured rat hippocampal neurons was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release methods as quantitative assays of cell death, and both methods indicated that propentofylline (PPF) had the ability to protect the neurons against the toxicity, although these two assay methods revealed different mechanisms for the toxic effect of beta42. Promotion of the active exocytotic system of the cells was suggested after treatment with beta42 in the MTT assay and in determination of 9-aminoacridine (AA) excretion from the preloaded cells after 24-h treatment with beta42. The promotion of AA exocytosis was blocked by the addition of PPF (20 microg/ml). The preventive effect of PPF on the neurotoxicity of beta42 has been proposed to be caused by elevation of the intracellular level of cAMP as a result of depression of the hydrolytic activity of cells.
Koriyama
Y
Y
Department of Biodynamics, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa, Japan.
Yamazaki
M
M
Chiba
K
K
Mohri
T
T
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; D014970:Xanthines; C075222:amyloid beta-protein (1-42); C032114:propentofylline; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue