beta-amyloid-induced endothelial necrosis and inhibition of nitric oxide production.
Deposits of amyloid beta-peptide (A beta) in senile plaques and cerebral blood vessels is the prominent feature of Alzheimer's disease (AD), regardless of genetic predisposition. The cellular origin of cerebral deposits of A beta or its precise role in the neurodegenerative process has not been established. Recently we demonstrated a novel action of beta-amyloid on blood vessels--vasoactivity and endothelial damage through superoxide radicals. Since endothelial dysfunction is associated with vascular degenerative diseases, we examined the direct action of A beta on endothelial cells in culture. Cells treated with A beta displayed characteristics of necrotic cell death which was prevented by the free radical scavenging enzyme superoxide dismutase. Stimulation of endothelial nitric oxide (NO) production by the calcium ionophore, A23187, or bradykinin was inhibited by beta-amyloid. We conclude that an imbalance of NO and oxygen radicals may mediate the A beta-induced endothelial damage on endothelial cells in culture and may also contribute to a variety of pathophysiological conditions associated with aging: hypertension, cerebral ischemia, vasospasm, or stroke.
Sutton
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ET
Department of Physiology and Biophysics, College of Medicine, University of South Florida, Tampa 33612, USA.
Hellermann
G R
GR
Thomas
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D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D009569:Nitric Oxide; D000001:Calcimycin; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester