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.

Figure 1

Cerebral microvessel and brain AβPP and BACE1 protein levels in wild type and eNOS^-/- mice treated with nitroglycerine or vehicle. (A) Western blot and densitometric analysis of (B) AβPP and (C) BACE1 were performed in cerebral microvessel tissue. (n=6-8, P<0.001). (D) Western blot and densitometric analysis of (E) AβPP and (F) BACE1 were performed in brain tissue. (n=6-10, P<0.001).

Figure 2

cGMP levels in the cerebral microvessels and brains of wild type and eNOS^-/- mice treated with nitroglycerine or vehicle. cGMP was measured via immunoassay in the cerebral microvessel of (A) wild type and (B) eNOS^-/- mice. cGMP measured in the brain tissue of (C) wild type and (D) eNOS^-/- animals. Data is presented as mean ± SD (n=6-7, P<0.01).