Novel differential interaction of TNF receptor subtypes with Alzheimer's amyloid-β-peptide signals neuron death and survival (original) (raw)

Poster Pre.rentation: Molecular and Cellular Biology IV s255 mediator of cellular processes and a major component of the constitutive immune response. We have previously shown that the enhancement of macrophage NO production is isoform specific with APOE4<APOE3. One potentxd site for modulation of NO production is the uptake of arginine, the substrate for nitric oxide synthase (NOS). Arginine tranrport is camed out by Na'-independent cationic transporterr (formerly known as y+ transporters) whose expression is tightly coupled to NOS expression. Usmg 'H+-arginine. we examined arginine uptake in microglia and neurons cultured from wild-type. APOE knockout mtce and mice made transgenic for the human APOE 3 or 4 allele on a mouse APOE knockout background. For micro&, the cells were pretreated with y-interferon (IFN) for 8 hours in IO or 100 FM arginine, washed and then treated for 4 hours with the double-stranded polyribonucleotide, Polyinosinic:Polycytidylic (PIG). or lipopolyaaccharide (LPS) followed by determinatton of arginine uptake. Neuron\ were not pretreated with $FN. Arginine transport was measured at physiological level\ of @nine and wa\ blocked by Gmultaneow treatment with N-monomethyl arginine (NMMA). Both PIC and LPS sigmficantly increased arginine transport compared to untreated conditions in microglia while PIC increased transport in neurons. Microglia and neurons from APOE 4 transgenic mace demonstrated a significantly higher level of arginine uptake