Endothelial cell dysfunction in response to intracellular overexpression of amyloid precursor protein.
Previous reports have shown that exposure of vascular endothelial and smooth muscle cells to exogenous amyloid beta (Abeta) peptide results in cell damage and toxicity via oxidative injury. In this study we demonstrate that overexpression of the amyloid precursor protein (APP) is toxic to bovine aortic endothelial cells but not to bovine aortic smooth muscle cells. Intracellular coexpression of the free radical scavenger proteins metallothionein or MnSOD abolished the toxic effect of APP overexpression in endothelial cells. Our results demonstrate that endothelial cells are specifically susceptible to intracellular overexpression of APP and free radical generation is the likely mechanism of cell damage due to APP overexpression.
Jahroudi
N
N
Department of Radiation Oncology, University of Pittsburgh Medical Center, Pennsylvania 15213, USA. jahroudi@vms.cis.pitt.edu
Kitney
J
J
Greenberger
J S
JS
Bowser
R
R
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011137:Polystyrenes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D011137:Polystyrenes; D012333:RNA, Messenger; D008668:Metallothionein; D013482:Superoxide Dismutase; C068153:superoxide dismutase-poly(styrene co-maleic acid butyl ester)