THE INTERACTION BETWEEN CHRONIC LOW-LEVEL LEAD AND THE AMYLOID-BETA PRECURSOR PROTEIN

Chronic low-level lead exposure is toxic to the developing nervous sys tem. The amyloid precursor protein (A beta PP) plays a pivotal role in this developmental process, both as a neurotrophic/neuroprotective fa ctor and as a mediator of cell adhesion. In this study, we have used a n in vitro system To examine the intel action between chronic low-leve l 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 1 0(-6)M) for 96 hours resulted in a 50% increase in the levels of the p articulate form of the protein with a parallel decrease in the soluble form (A beta PP). This effect of lead was reversible following the re moval of the the toxin. This increase in membrane-bound A beta PP was also paralleled by an increase in cell adhesivity to a fibronectin sub strate. In addition A beta PPs also acted to attenuate lend 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 act ion within the cell.