Retinoic acid induced differentiated neuroblastoma cells show increased expression of the beta A4 amyloid gene of Alzheimer's disease and an altered splicing pattern.
Retinoic acid (RA) induced differentiation of SH-SY5Y neuroblastoma cells is associated with more than a tenfold induction of total Alzheimer's disease beta A4 amyloid protein precursor (APP) mRNA as analyzed by Northern blot hybridisation. S1 nuclease protection experiments reveal that the splicing pattern of these differentiated cells is altered in favor of APP695 mRNA, coding for the shortest amyloidogenic beta A4 amyloid precursor protein. Induction of differentiation of SH-SY5Y cells with NGF leads to a fivefold increase of total APP mRNA without change in the splicing pattern. This suggests that RA but not NGF induces factor(s) which are responsible for an APP hnRNA splicing favoring APP695 mRNA.
Center for Molecular Biology (ZMBH), University of Heidelberg, FRG.
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König
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Masters
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Beyreuther
D000544:Alzheimer Disease / Q000235:genetics*; D000682:Amyloid / Q000235:genetics*; D016229:Amyloid beta-Peptides; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D015246:Deoxyribonuclease EcoRI; D005796:Genes / Q000187:drug effects*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D012326:RNA Splicing / Q000187:drug effects*; D012334:RNA, Neoplasm / Q000235:genetics*; D015183:Restriction Mapping; D014212:Tretinoin / Q000494:pharmacology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D012334:RNA, Neoplasm; D014212:Tretinoin; D015246:Deoxyribonuclease EcoRI