Starvation triggers Abeta42 generation from human umbilical vascular endothelial cells.
Cerebral amyloid angiopathy is a common feature in Alzheimer's disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Abeta(42) under starvation. Starvation can increase the secretion of Abeta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Abeta(42) produced under starvation in HUVECs. These results suggest that starvation-induced Abeta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD.
Ma
Jian-Fang
JF
Department of Neurology & Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Wang
Hong-Mei
HM
Li
Qing-Yun
QY
Zhang
Yu
Y
Pan
Jing
J
Qiang
Qiang
Q
Xin
Xiao-Yu
XY
Tang
Hui-Dong
HD
Ding
Jian-Qing
JQ
Chen
Sheng-Di
SD
D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013217:Starvation / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D014472:Umbilicus
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D053829:Amyloid Precursor Protein Secretases