title: Supplementation of nitric oxide attenuates AβPP and BACE1 protein in cerebral microcirculation of eNOS-deficient mice.
abstract: Recently, we demonstrated in endothelial nitric oxide synthase deficient (eNOS-/-) mice that loss of endothelial NO led to increased protein levels of amyloid-β protein precursor (AβPP), β-site AβPP cleaving enzyme 1 (BACE1), and amyloid-β (Aβ) peptide. Therefore, our aim was to determine if NO supplementation in vivo would attenuate AβPP and BACE1 protein levels. cGMP levels were significantly increased while AβPP and BACE1 protein levels were statistically lower in cerebral microvessels from nitroglycerin-treated eNOS-/- mice as compared to vehicle-treated mice. Our findings support the concept that preservation of NO/cGMP signaling is an important modulator of expression and processing of AβPP.
authors.affiliation: Department of Anesthesiology and Molecular Pharmacology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Austin
authors.forename: Livius V
authors.initials: LV
authors.lastname: d'Uscio
authors.forename: Zvonimir S
authors.initials: ZS
authors.lastname: Katusic
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000235:genetics; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000235:genetics; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D005996:Nitroglycerin / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D005996:Nitroglycerin; D006152:Cyclic GMP