Xs. Wang et E. Gruenstein, RAPID ELEVATION OF NEURONAL CYTOPLASMIC CALCIUM BY APOLIPOPROTEIN-E PEPTIDE, Journal of cellular physiology, 173(1), 1997, pp. 73-83
Apolipoprotein E (apoE) and certain peptides derived from it have been
shown to exert neurotoxic effects in vitro, and apoE has been linked
to the etiology of Alzheimer's disease. The mechanisms underlying thes
e toxic and pathological effects are, however, not known. To approach
this question, we have studied the effects of apoE peptides on the cyt
oplasmic calcium ([Ca2+](i)) homeostasis of cultured cortical neurons.
A tandem dimer repeat peptide (apoE(dp)) derived from the receptor bi
nding domain of apoE was found to have a potent effect on elevation of
[Ca2+](i) calcium. The pathway by which apoE(dp) exerted this effect
was shown to involve both the mobilization of intracellular calcium an
d the influx of extracellular calcium, although the effect on influx w
as more pronounced. Calcium mobilization occurs via a G-protein-linked
phospholipase C (PLC) pathway, whereas calcium influx appears to invo
lve a novel Co2+-sensitive channel. Both the mobilization and the infl
ux of calcium require the binding of the apoE peptide to a membrane re
ceptor because both pathways are blocked by antibody to low-density-li
poprotein receptor-related protein. The data suggest that the neurotox
ic effects of apoE may be mediated by a persistent elevation of [Ca2+]
(i). (C) 1997 Wiley-Liss, Inc.