Heat shock alters Alzheimer's beta amyloid precursor protein expression in human endothelial cells.
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.
Ciallella
J R
JR
Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington.
Rangnekar
V V
VV
McGillis
J P
JP
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
D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger