The interaction between chronic low-level lead and the amyloid beta precursor protein.
Chronic low-level lead exposure is toxic to the developing nervous system. The amyloid beta precursor protein (A beta PP) plays a pivotal role in this developmental process, both as a neurotrophic/neuroprotective factor and as a mediator of cell adhesion. In this study, we have used an in vitro system to examine the interaction between chronic low-level lead and the expression and function of A beta PP. Chronic exposure of the HN9 mouse hippocampal cell line to lead chloride (10(-14) M to 10(-6) M) for 96 hours resulted in a 50% increase in the levels of the particulate form of the protein with a parallel decrease in the soluble form (A beta PP). This effect of lead was reversible following the removal of the toxin. This increase in membrane-bound A beta PP was also paralleled by an increase in cell adhesivity to a fibronectin substrate. In addition, A beta PP also acted to attenuate lead toxicity. Cells which secreted high levels of the protein were resistant to lead toxicity when compared with control cells suggesting that the protein may be acting to chelate the metal and thus attenuating its toxic action within the cell.
Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Scotland, UK.
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D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D002908:Chronic Disease; D007855:Lead Poisoning / Q000378:metabolism*; D016015:Logistic Models; D051379:Mice
D016564:Amyloid beta-Protein Precursor; D002413:Cations, Divalent