NR AJCA
AU Östlund,P.; Lindegren,H.; Pettersson,C.; Bedecs,K.
TI Up-regulation of functionally impaired insulin-like growth factor-1 receptor in scrapie-infected neuroblastoma cells
QU The Journal of Biological Chemistry 2001 Sep 28; 276(39): 36110-5
PT journal article
AB A growing body of evidence suggests that an altered level or function of the neurotrophic insulin-like growth factor-1 receptor (IGF-1R), which supports neuronal survival, may underlie neurodegeneration. This study has focused on the expression and function of the IGF-1R in scrapie-infected neuroblastoma cell lines. Our results show that scrapie infection induces a 4-fold increase in the level of IGF-1R in two independently scrapie-infected neuroblastomas, ScN2a and ScN1E-115 cells, and that the increased IGF-1R level was accompanied by increased IGF-1R mRNA levels. In contrast to the elevated IGF-1R expression in ScN2a, receptor binding studies revealed an 80% decrease in specific (125)I-IGF-1-binding sites compared with N2a cells. This decrease in IGF-1R-binding sites was shown to be caused by a 7-fold decrease in IGF-1R affinity. Furthermore, ScN2a showed no significant difference in IGF-1 induced proliferative response, despite the noticeable elevated IGF-1R expression, putatively explained by the reduced IGF-1R binding affinity. Additionally, IGF-1 stimulated IGF-1Rbeta tyrosine phosphorylation showed no major change in the dose-response between the cell types, possibly due to altered tyrosine kinase signaling in scrapie-infected neuroblastoma cells. Altogether these data indicate that scrapie infection affects the expression, binding affinity, and signal transduction mediated by the IGF-1R in neuroblastoma cells. Altered IGF-1R expression and function may weaken the trophic support in scrapie-infected neurons and thereby contribute to neurodegeneration in prion diseases.
MH Animal; Binding Sites; Brain Neoplasms/*metabolism; Cell Division; Coculture; Dose-Response Relationship, Drug; Human; Kinetics; Mice; Neuroblastoma/*metabolism; Phosphorylation; Precipitin Tests; Protein Binding; Receptor, IGF Type 1/*chemistry/*metabolism; Reverse Transcriptase Polymerase Chain Reaction; Scrapie/*metabolism; Support, Non-U.S. Gov't; Time Factors; Tumor Cells, Cultured; Tyrosine/metabolism; *Up-Regulation
AD Department of Neurochemistry and Neurotoxicology, University of Stockholm, Svante Arrhenius v. 21A, S-10691 Stockholm, Sweden.
SP englisch
PO USA