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Analysis of a Novel Mechanism of Neuronal Toxicity Produced by an Apolipoprotein E‐Derived Peptide
Author(s) -
Moulder Krista L.,
Narita Masaaki,
Chang Louis K.,
Bu Guojun,
Johnson Eugene M.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0721069.x
Subject(s) - apolipoprotein e , neurotoxicity , toxicity , programmed cell death , dna fragmentation , apoptosis , biology , endocrinology , receptor , caspase , medicine , superior cervical ganglion , pharmacology , biochemistry , disease
: The apolipoprotein E (apoE)‐derived peptide(141‐155) 2 has a neurotoxic effect, implying that apoE itself couldbe a source of toxicity in Alzheimer's disease brain. We characterized thetoxicity of this peptide on superior cervical ganglion (SCG) neurons andcompared the death with the apoptotic death that occurs after nerve growthfactor (NGF) deprivation in these cells. A dose of 10 μM apoE(141‐155) 2 resulted in the death of ~50% of the neurons within 24h. Nuclear condensation and DNA fragmentation preceded the death. However,most inhibitors of NGF deprivation‐induced death, including the caspaseinhibitor Boc‐aspartyl( O ‐methyl)fluoromethyl ketone and geneticdeletion of bax ‐1‐ , had no effect on the toxicity.Inclusion of depolarizing levels of potassium did block the toxicity.Receptor‐associated peptide (RAP), an antagonist for apoE receptors, did notprotect cells in either SCG or hippocampal cultures. In addition, RAP had noeffect on internalization of the apoE peptide. These data support theobservation that apoE (141‐155) 2 is neurotoxic but suggest that the neurotoxicity is distinct from classical apoptosis or necrosis. Furthermore, these results indicate that the toxic effect may occur independently of members of the low‐denśity lipoprotein receptor gene family.