Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Abstract

Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of NO compared to apoE3. Prior to biochemical investigations, we have quantified the expression of several candidate receptor genes, including low-density lipoprotein (LDL)-receptor family members and scavenger receptor class B, types I and II (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38 human cell lines, of which 12 derive from brain. Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Yand CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma and IMR-32 neuroblastoma cells. Transcripts of the other lipoprotein receptors were widely, but variably, distributed across the different cell types. Of particular note was the predominant expression of SR-BII over SR-BI in many of the brainderived cells. As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor.

Role of ABCG1 and ABCA1 in Regulation of Neuronal Cholesterol Efflux to Apolipoprotein E Discs and Suppression of Amyloid-β Peptide Generation

“…Previous studies indicate that reconstituted apoE discs (containing PL and cholesterol comparable with the discs used in the present work) promote cellular cholesterol efflux through scavenger receptor class B type I (62). This pathway is not likely to contribute to neuronal cholesterol efflux as we could find no evidence for scavenger receptor class B type I expression in either primary neurons or neuronal cell lines 5 ; a finding consistent with previous work (63). Our data indicate that efflux of unmodified cholesterol from neurons to apoE discs exceeds the amount of cholesterol released through a pathway that relies on conversion of cholesterol to a more polar product, such as 24-OH-Ch, that could exit the cell membrane by diffusion (i.e.…”

Interferon decreases expression of human scavenger receptor class BI, a possible HCV receptor in hepatocytes

“…A recent report demonstrates that HCV soluble E2 can interact with not only human SR-BI but also SR-BII 32. Previous reports showed that SR-BII is expressed at a relatively high baseline level in rat liver, HepG2 and other cells 33 34. In this study, we revealed that IFNα decreased SR-BI mRNA expression but it did not affect SR-BII mRNA.…”

Deletion of Apolipoprotein E Receptor-2 in Mice Lowers Brain Selenium and Causes Severe Neurological Dysfunction and Death When a Low-Selenium Diet Is Fed

“…Although there is controversy over which cells express apoER2 in the brain, it is generally agreed that the receptor is present on neurons (D' Arcangelo et al, 1999;Trommsdorff et al, 1999) and on some glial cells that are neuron precursors (Hartfuss et al, 2003;Thilakawardhana et al, 2005). There is little evidence that apoER2 is present at the blood-brain barrier.…”