Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein.
Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal cortex, significantly declines with advanced age. We have previously demonstrated that DHEA prevents the reduction in non-amyloidogenic APP processing, following prolonged stimulation of the muscarinic receptor, in PC12 cells that express the ml acetylcholine-receptor. The present study examined whether this effect may be mediated via modulation of APP metabolism. It was found that DHEA treatment increases the content of membrane-associated APP holoprotein by 24%, and the accumulation of secreted APP in the medium by 63%. No increase in viable cell number nor in nonspecific protein production was observed in DHEA-treated cells. Thus, DHEA seems to increase specifically both APP synthesis and secretion. We propose that the age-associated decline in DHEA levels may be related to the pathological APP metabolism observed in Alzheimer's disease.
Danenberg
H D
HD
Department of Organic and Medicinal Chemistry, Israel Institute for Biological Research, Ness-Ziona, Israel.
Haring
R
R
Fisher
A
A
Pittel
Z
Z
Gurwitz
D
D
Heldman
E
E
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D016716:PC12 Cells; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D003687:Dehydroepiandrosterone; D011493:Protein Kinase C; C070515:bisindolylmaleimide I