Transforming growth factors-beta protect primary rat hippocampal neuronal cultures from degeneration induced by beta-amyloid peptide.
Treatment of primary rat embryo hippocampal neuronal cultures with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a 60% decrease in cell viability as determined by MTT incorporation. When these cells were treated with 0.1-10 ng/ml of either transforming growth factor-beta (TGF-beta) 1, 2 or 3 for 24 h before exposure to A beta P, there was a 2.9-, 1.9-, and 3.2-fold increase in cell survival, respectively, compared to cells treated with A beta P alone. The viability of cells treated with A beta P and 0.1-10 ng/ml TGF-beta was comparable to that of cells not treated with A beta P. The protective effects were less pronounced at lower TGF-beta concentrations. The protective effects of pretreatment with TGF-beta were less striking in mouse CCL-N-2a and human SK-N-SH neuroblastoma cell lines. When all cells were treated with TGF-beta for 24 h following a 24 h exposure to A beta P, there was a trend toward increased cell viability which was less significant than pretreatment with TGFs-beta. An isoform-specific TGF-beta SELISA showed that primary hippocampal neuronal cultures and the neuroblastoma cell lines secrete all 3 TGF-beta isoforms. Based on our results, we propose that the increased expression of TGF-beta observed in brains of patients with Alzheimer's disease may offer some degree of neuroprotection.
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA.
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Ren
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Flanders
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005333:Fetus; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D009498:Neurotoxins; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C074636:amyloid beta-protein (25-35)