Transforming growth factor-β protects human hNT cells from degeneration induced by β-amyloid peptide: involvement of the TGF-β type II receptor
Post-mitotic, human neurons (hNT cells) which have a phenotype similar to that of terminally differentiated neurons of the central nervous system were generated by treating the NT2/D1 human teratocarcinoma cell line with retinoic acid. Treatment of both hNT and NT2/D1 cells with 10−5 M β-amyloid peptide fragment 25–35 (AβP) for 24 h resulted in a decrease in cell viability as determined by MTT incorporation and Trypan blue exclusion, and also induced an apoptotic morphology in hNT cells. Pre-treatment of cells for 24 h with 10 ng/ml TGF-β 1 or 2 before addition of AβP reduced the apoptotic morphology of hNT cells and increased cell viability in hNT cells, but not in NT2/D1 cells. Results of RT-PCR, immunohistochemistry and analysis of receptor cross-linking of [125I]TGF-β1 to the cell membrane, all showed that the TGF-β type II receptor is expressed by hNT cells, but not NT2/D1 cells. These results suggest that TGF-β can protect human, terminally differentiated, TGF-β type II receptor-positive neurons from AβP toxicity. We propose that the increased expression of TGF-β in brains of patients with Alzheimer's disease may offer some degree of neuroprotection if neurons also express a functional TGF-β type II receptor.