Amyloid β Protein (25–35) Stimulation of Phospholipase C in LA-N-2 Cells |
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Authors: | Indrapal N Singh Giuseppe Sorrentino Julian N Kanfer |
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Institution: | Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, Canada;and; Istituto di Scienze Neurologiche, Facoltàdi Medicina, Seconda Universitàdi Napoli, Napoli, Italy |
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Abstract: | Abstract: The amyloid β protein (25–35) stimulated appearance of 3H-inositol phosphates from 3H]inositol-prelabeled LA-N-2 cells was investigated. This stimulation was unaltered by extra- and intracellular calcium chelators in a calcium-free medium or by several protein kinase inhibitors. This phospholipase C stimulation by amyloid β protein appeared to be pertussis toxin sensitive. It is possible that this phospholipase C stimulation by amyloid β protein is a receptor-mediated process. This possibility is based on two related observations. The stimulation is ablated by the presence of conventional antagonists for metabotropic, adrenergic, and bombesin agonists. The IC50 values were 12 µ M for propranolol, 15 µ M for AP-3, and 25 n M for Tyr4, d -Phe12]bombesin. Additional support comes from results of densensitization and resensitization experiments. Amyloid β protein stimulation of phospholipase C was absent from LA-N-2 cells previously treated with norepinephrine, trans -1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), bombesin, or amyloid β peptide. In a similar manner, LA-N-2 cells previously treated with amyloid β protein were no longer responsive to norepinephrine, t-ACPD, or bombesin. The responsiveness to amyloid β protein returned, subsequent to a period of resensitization for the individual agonists. It is suggested that this observed amyloid β protein stimulation of phospholipase C may be responsible for the elevated quantity of inositol seen in the brains of Alzheimer's disease patients. |
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Keywords: | Alzheimer's disease Amyloid β protein Phospholipase C Receptor-mediated Inositol phosphates |
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