TY - JOUR
T1 - Interaction of beta-amyloid peptides with integrins in a human nerve cell line
AU - Sabo, S.
AU - Lambert, M. P.
AU - Kessey, K.
AU - Wade, W.
AU - Krafft, G.
AU - Klein, William L
PY - 1995/1/16
Y1 - 1995/1/16
N2 - β-Amyloid accumulates as extracellular aggregates in Alzheimer's-afflicted brain tissue, but it also is secreted by healthy tissue, for reasons not yet established. One possibility is that β-amyloid, which contains a sequence (RHDS) homologous to the cell-binding domain of fibronectin, may modulate integrin function, a possibility supported by previous data from non-neuronal cells (Ghiso et al., Biochem. J., 288 (1992) 1053-1059). The current work shows that functional interaction with β-amyloid peptides is also supported by integrins in neuronal cells. Experiments used the SH-SY5Y human neuroblastoma cell line, which was shown to contain integrins that mediated cell adhesion to substratum-bound fibronectin. Adhesion to fibronectin was partially blocked by synthetic β-amyloid peptides containing the RHDS sequence. β-Amyloid sequences adsorbed to substratum themselves were found to mediate cell adhesion, although less effectively than fibronectin. Anti-integrin blocked the peptide-mediated adhesion, at doses commensurate with those blocking fibronectin-mediated adhesion. The data support the hypothesis that β-amyloid peptides could physiologically, and perhaps pathogenically, modulate the activity of neuronal integrins, important cell surface receptors known to control protein kinase activities, Ca2+ levels, gene expression and organization of the cytoskeleton.
AB - β-Amyloid accumulates as extracellular aggregates in Alzheimer's-afflicted brain tissue, but it also is secreted by healthy tissue, for reasons not yet established. One possibility is that β-amyloid, which contains a sequence (RHDS) homologous to the cell-binding domain of fibronectin, may modulate integrin function, a possibility supported by previous data from non-neuronal cells (Ghiso et al., Biochem. J., 288 (1992) 1053-1059). The current work shows that functional interaction with β-amyloid peptides is also supported by integrins in neuronal cells. Experiments used the SH-SY5Y human neuroblastoma cell line, which was shown to contain integrins that mediated cell adhesion to substratum-bound fibronectin. Adhesion to fibronectin was partially blocked by synthetic β-amyloid peptides containing the RHDS sequence. β-Amyloid sequences adsorbed to substratum themselves were found to mediate cell adhesion, although less effectively than fibronectin. Anti-integrin blocked the peptide-mediated adhesion, at doses commensurate with those blocking fibronectin-mediated adhesion. The data support the hypothesis that β-amyloid peptides could physiologically, and perhaps pathogenically, modulate the activity of neuronal integrins, important cell surface receptors known to control protein kinase activities, Ca2+ levels, gene expression and organization of the cytoskeleton.
KW - Adhesion
KW - Alzheimer's
KW - Amyloid
KW - Fibronectin
KW - Laminin
KW - Neuroblastoma
KW - SH-SY5Y
UR - http://www.scopus.com/inward/record.url?scp=0028944873&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028944873&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(94)11159-G
DO - 10.1016/0304-3940(94)11159-G
M3 - Article
C2 - 7739799
AN - SCOPUS:0028944873
VL - 184
SP - 25
EP - 28
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -