HEAT-SHOCK ALTERS ALZHEIMERS BETA-AMYLOID PRECURSOR PROTEIN EXPRESSION IN HUMAN ENDOTHELIAL-CELLS

One of the pathological lesions in Alzheimer's disease (AD) is the amy loid or senile plaque. The plaque core is predominantly made up of amy loid beta peptide (A beta), a 42-43 amino acid peptide derived from am yloid precursor protein (APP). APP is a membrane bound glycoprotein wh ich is expressed ubiquitously in many cells. Although normal or pathol ogical 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 an d endothelial cells, it can inhibit a blood coagulation factor, and se creted APP can be neuroprotective. Changes in expression of APP during cellular stress or inflammation may contribute to pathological deposi tion of A beta. In the present studies, expression of APP in human end othelial cells was examined following heat shock. In human umbilical v ein endothelial cells (HUVECs) exposed to 42 degrees C for 30 min, the re 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 p rotein immunoreactivity in the cytoplasm in a perinuclear Golgi-like r egion, and in discrete granular cytoplasmic structures. Immunoblot ana lysis 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 upregula tion of APP mRNA and protein supports a cellular stress role for APP. (C) 1994 Wiley-Liss, Inc.