Changes in morphology of neuroblastoma cells treated with all-trans retinoic acid combined with transfer of the C-terminal region of the amyloid precursor protein.
Alzheimer disease is a progressive neurodegenerative disorder that is characterized by a loss of cognitive and memory functions. Amyloid fibrils deposited in neuritic plaque is mainly beta-amyloid protein (Abeta) that is derived from amyloid precursor protein (APP). The secreted form of APP, which is corresponded to N-terminal portion of APP, shows neurotrophic activities. On the other hand, Abeta and cytoplasmic domains of APP are thought to be neurotoxic. In order to investigate the effect of C-terminal fragment of APP covering Abeta and the cytoplasmic domain upon cell growth and differentiation, we established a stably transfected cell line producing the C-terminal 100 amino acid peptide of APR The transfected clones stained positively with anti-Abeta monoclonal antibody, TB-1. The growth rate of the transfected cells was not significantly different from that of mock-transfected cells or native NB39 cells. After treatment with all-trans retinoic acid (ATRA), mock-transfected cells extended neurite processes and showed neuronal-like differentiation, while a transfected clone overexpressing C-terminal fragment did not present neuronal-like morphology. These results suggest that ATRA-induced neurite extension may be suppressed by overexpression of the C-terminal fragment of APP.
Honda
S
S
First Department of Internal Medicine, Sapporo Medical University, Japan.
Itoh
F
F
Yoshimoto
M
M
Hinoda
Y
Y
Imai
K
K
D016229:Amyloid beta-Peptides / Q000737:chemistry; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D001921:Brain / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000473:pathology*; D014162:Transfection / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014212:Tretinoin