PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 8495367

Decrease in amyloid precursor protein precedes hippocampal degeneration in rat brain following transient global ischemia.

P M Robison·J A Clemens·E B Smalstig·D Stephenson·P C May
View original source ↗Export metadata ↓

Abstract

We have studied amyloid precursor protein (APP) expression in rat brain following transient global ischemia. Ischemic damage 24 h after 30 min of four-vessel occlusion (4VO) was limited to the caudate nucleus; hippocampal pyramidal neurons appeared histologically normal by light microscopy. Consistent with ongoing neurodegeneration in the caudate nucleus, microtubule-associated protein-2 (MAP-2) levels assessed by immunoblots were significantly reduced in homogenates of caudate nucleus after 4VO. MAP-2 levels In the hippocampus were comparable to control values. In contrast, full length APP levels in both the caudate nucleus and hippocampal homogenates were significantly decreased following 4VO despite normal hippocampal morphology at 24 h. These findings suggest that decrements in full length APP precede overt neuronal damage and may play a role in the subsequent delayed neurodegeneration in the hippocampus.

Explore related subjects

Amyloid beta-Protein PrecursorAnimalsCaudate NucleusHippocampusImmunoblottingIschemic Attack, TransientMaleMicrotubule-Associated ProteinsNerve DegenerationRatsRats, WistarJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P M Robison, J A Clemens, E B Smalstig, D Stephenson, P C May. 1993-04-16. Decrease in amyloid precursor protein precedes hippocampal degeneration in rat brain following transient global ischemia.. https://doi.org/10.1016/0006-8993(93)91475-8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1996

The initiator element and proximal upstream sequences affect transcriptional activity and start site selection in the amyloid beta-protein precursor promoter.

The TATA-less human amyloid beta-protein precursor promoter contains an initiator element with the sequence CGTCA+1GTT. Primary transcriptional start sites were identified at positions +1 and -4. Deletion of the upstream activator elements APBbeta and APBalpha did not affect the selection of transcriptional start sites, although total transcriptional activity was reduced both in vitro and in vivo. Mutations within the initiator element shifted the transcriptional start sites and reduced transcriptional activity. Mutations between positions -6 and -35 changed the relative utilization of start sites +1 and -4 without affecting the total level of transcriptional activity. A 10-base pair deletion between position -40 and -31 increased in vitro transcriptional activity with a preeminent utilization of the start site at position -4. In contrast, a 20-base pair deletion between position -40 and -21 resulted in a reduction in transcriptional activity and in the primary utilization of the start site at position +1. Furthermore, transactivation by APBbeta and APBalpha was eliminated. DNase I footprinting provided evidence for the existence of two binding domains designated UE (position -12 to -30) and Inr (position +7 to -7). The positions of these binding domains are altered in mutations and deletions that affect transcriptional activity.

Amyloid beta-Protein Precursor↗
PubMed1996

Alzheimer's amyloid precursor protein is expressed on the surface of hematopoietic cells upon activation.

A4-amyloid is the major component of senile plaques and neurofibrillary tangles found in the brain of patients suffering Alzheimer's disease. This 39-42 amino acid peptide is derived from a larger precursor protein (APP). Since APP gene encodes for a putative membrane protein, the study of APP expression at the cell surface may provide useful data for understanding its physiological function. In this report, we present data on APP expression, that was detected by APP specific mAbs in cells of the hematopoietic system. APP was weakly expressed on the cell surface of resting human lymphocytes and monocytes, but it could be induced to the surface of those cells upon stimulation. The cell activators capable of inducing APP membrane expression comprehended mitogenic lectins, calcium ionophores, phosphatase inhibitors, and anti mu-chain or anti-CD3 antibodies in B and T cells, respectively. Interestingly, phorbol esters were able to induce APP membrane expression in monocytic, but not in lymphoid cells. In contrast to lymphocytes and monocytes, granulocytes never expressed cell surface or cytoplasmic APP, even after the activation. The induction of membrane APP in response to lymphocyte activation signals, including antibodies to the antigen receptor of B and T cells, raises the possibility that APP might play the role of a cell surface receptor in the immune system.

Amyloid beta-Protein Precursor↗
PubMed1996

APPL, the Drosophila member of the APP-family, exhibits differential trafficking and processing in CNS neurons.

The Drosophila Appl gene encodes a transmembrane protein that is expressed exclusively in neurons. Amino acid comparisons show that APPL protein is a member of the amyloid precursor protein (APP)-like family of proteins. Similar to mammalian APP-family proteins, APPL is synthesized as a transmembrane holoprotein and cleaved to release a large secreted amino-terminal domain. Using immunocytochemical methods, we have analyzed the distribution of APPL in the Drosophila CNS. Surprisingly, although APPL is present in all neuronal cell bodies, the neurophil shows sterotypic differential distribution. Double-labeling experiments with different neuronal markers were used to distinguish between APPL associated with neuronal processes or extracellular matrix. The distribution of APPL protein produced from transgenes encoding wild-type (APPL), secretion-defective (APPLsd), and constitutively secreted (APPLs) forms was analyzed in an Appl-deficient background to determine which APPL form is associated with different neuropil regions. We found that APPLsd protein is enriched where APPL immunoreactivity coincides with neuronal processes. In contrast, APPLs preferentially localizes to those parts of the neuropil that show a diffuse APPL signal that rarely colocalizes with processes, and thus seems to be a component of the extracellular matrix. These data indicate that proteolytic cleavage and trafficking of APPL is differentially regulated in different neuronal populations. Through metamorphosis, APPL is especially abundant in growing axons and in areas where synapses are forming. Interestingly, in adult brains, APPL protein is enriched in the mushroom bodies and to a lesser extent in the central complex, structures involved in learning and memory.

Amyloid beta-Protein Precursor↗