Amyloid-β(25-35), an amyloid-β(1-42) surrogate, and proinflammatory cytokines stimulate VEGF-A secretion by cultured, early passage, normoxic adult human cerebral astrocytes

Journal of Alzheimer's Disease : JAD
Anna ChiariniIlaria Dal Prà

Abstract

Cerebrovascular angiopathy affects late-onset Alzheimer's disease (LOAD) brains by possibly increasing vascular endothelial growth factor (VEGF). A expression, thereby stimulating endothelial cell proliferation and migration. Indeed, VEGF-A gene upregulation, with increased VEGF-A protein content of reactive astrocytes and microglia, occurs in LOAD brains, and neovascularization was observed one week after injecting amyloid-β (Aβ)(1-42) into rat hippocampus. We have now found, with cultured 'normoxic' normal adult human astrocytes (NAHAs), that fibrillar Aβ(25-35) (an active Aβ(1-42) fragment) or a cytokine mixture (the (CM)-trio (interleukin [IL]-1β+interferon [IFN]-γ+tumor necrosis factor [TNF]-α), or pair (IFN-γ+TNF-α) like those produced in LOAD brains) stimulates the nuclear translocation of stabilized hypoxia-inducible factor (HIF)-1α protein and its binding to VEGF-A hypoxia-response elements; the mRNA synthesis for three VEGF-A splice variants (121, 165, 189); and the secretion of VEGF-A165. The CM-trio was the most powerful stimulus, IFN-γ+TNF-α was less potent, and other cytokine pairs or single cytokines or Aβ(35-25) were ineffective. While Aβ(25-35) did not change HIF-1β protein levels, the CM-trio increased both HI...Continue Reading

Citations

Mar 13, 2015·Iranian Red Crescent Medical Journal·Reza NajafipourHosein Afshar
May 21, 2016·Frontiers in Physiology·Anna ChiariniIlaria Dal Prà
Dec 12, 2017·Journal of Alzheimer's Disease : JAD·Rachel HarrisSeth Love
Nov 6, 2012·International Journal of Molecular Medicine·Ubaldo ArmatoJames F Whitfield
Oct 17, 2017·Frontiers in Cellular Neuroscience·Elise C OhkiRichard C Chou
Mar 24, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Abebe MucheReinhard Schliebs
Apr 29, 2015·Annals of Neurology·Han-Yun HsiaoYijuang Chern
May 30, 2017·Homeopathy : the Journal of the Faculty of Homeopathy·Clara BonafiniPaolo Bellavite
Feb 24, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Henning J DrewsLusine Danielyan
Nov 14, 2019·Frontiers in Pharmacology·Ilaria Dal PràAnna Chiarini
Apr 18, 2014·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Ilaria Dal PràUbaldo Armato
Apr 30, 2016·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J B ZhangP F Wang
Aug 23, 2016·Biochemical and Biophysical Research Communications·Alexei VerkhratskyRobert Zorec

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