title: Heat shock alters Alzheimer's beta amyloid precursor protein expression in human endothelial cells.
abstract: One of the pathological lesions in Alzheimer's disease (AD) is the amyloid or senile plaque. The plaque core is predominantly made up of amyloid beta peptide (A beta), a 42-43 amino acid peptide derived from amyloid precursor protein (APP). APP is a membrane bound glycoprotein which is expressed ubiquitously in many cells. Although normal or pathological functions for APP are not well understood, several observations suggest that APP may play a role in cellular stress and inflammation at the endothelial cell/vascular barrier. APP is found in platelets and endothelial cells, it can inhibit a blood coagulation factor, and secreted APP can be neuroprotective. Changes in expression of APP during cellular stress or inflammation may contribute to pathological deposition of A beta. In the present studies, expression of APP in human endothelial cells was examined following heat shock. In human umbilical vein endothelial cells (HUVECs) exposed to 42 degrees C for 30 min, there was a five- to eight-fold increase in APP mRNA levels which peaked at 4 hr. The increase in APP mRNA was followed by an increase in APP protein immunoreactivity in the cytoplasm in a perinuclear Golgi-like region, and in discrete granular cytoplasmic structures. Immunoblot analysis of APP in the cell media found a transient increase in APP which peaked at 1 hr after heat shock. These results suggest that cellular stress induces the secretion of APP from endothelial cells followed by a subsequent increase in APP mRNA and protein synthesis. The upregulation of APP mRNA and protein supports a cellular stress role for APP.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington.
authors.forename: J R
authors.initials: JR
authors.lastname: Ciallella
authors.forename: V V
authors.initials: VV
authors.lastname: Rangnekar
authors.forename: J P
authors.initials: JP
authors.lastname: McGillis
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013696:Temperature; D014158:Transcription, Genetic; D014471:Umbilical Veins / Q000187:drug effects / Q000201:enzymology
chemical_list: D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger