Influence of Nitric Oxide-Cyclic GMP and Oxidative STRESS on Amyloid-β Peptide Induced Decrease of Na,K-ATPase Activity in Rat Hippocampal Slices

E M Kawamoto; M M Cararo-Lopes; P F Kinoshita; L E M Quintas; L S Lima; D Z Andreotti; C Scavone

doi:10.1007/s00232-021-00196-9

Influence of Nitric Oxide-Cyclic GMP and Oxidative STRESS on Amyloid-β Peptide Induced Decrease of Na,K-ATPase Activity in Rat Hippocampal Slices

J Membr Biol. 2021 Dec;254(5-6):463-473. doi: 10.1007/s00232-021-00196-9. Epub 2021 Jul 29.

Authors

E M Kawamoto¹, M M Cararo-Lopes², P F Kinoshita², L E M Quintas³, L S Lima², D Z Andreotti^{1

2}, C Scavone⁴

Affiliations

¹ Laboratory of Molecular and Functional Neurobiology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
² Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
³ Laboratory of Biochemical and Molecular Pharmacology, Institute of Biomedical Sciences, Health Sciences Centre Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
⁴ Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. criscavone@usp.br.

PMID: 34327545
DOI: 10.1007/s00232-021-00196-9

Abstract

Amyloid-β peptide (Aβ) has been shown to cause synaptic dysfunction and can render neurons vulnerable to excitotoxicity and oxidative stress. Na,K-ATPase plays an important role to maintain cell ionic equilibrium and it can be modulated by N-methyl-D-aspartate (NMDA)-nitric oxide (NO)-cyclic GMP pathway. Disruption of NO synthase (NOS) activity and reactive oxygen species (ROS) production could lead to changes in Na,K-ATPase isoforms' activities that may be detrimental to the cells. Our aim was to evaluate the signaling pathways of Aβ in relation to NMDA-NOS-cyclic GMP versus oxidative stress on α₁-/α_2,3-Na,K-ATPase activities in rat hippocampal slices. Aβ_1-40 induced a concentration-dependent increase of NOS activity and increased cyclic guanosine monophosphate (cGMP), TBARS (thiobarbituric acid reactive substances), and 3-Nitrotyrosine (3-NT)-modified protein levels in rat hippocampal slices. The increase in NOS activity and cyclic GMP levels induced by Aβ_1-40 was completely blocked by MK-801 (inhibitor of NMDA receptor) and L-NAME (inhibitor of NOS) pre-treatment but changes in TBARS levels were only partially blocked by both compounds. The Aβ treatment also decreased Na,K-ATPase activity which was reverted by N-nitro-L-arginine methyl ester hydrochloride (L-NAME) but not by MK-801 pre-treatment. The decrease in enzyme activity induced by Aβ was isoform-specific since only α₁-Na,K-ATPase was affected. These findings suggest that the activation of NMDA-NOS signaling cascade linked to α_2,3-Na,K-ATPase activity may mediate an adaptive, neuroprotective response to Aβ in rat hippocampus.

Keywords: Amyloid-β peptide; Glutamate; Na,K-ATPase; Nitric oxide; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cyclic GMP
Dizocilpine Maleate
Hippocampus*
N-Methylaspartate
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide
Oxidative Stress*
Peptides
Rats
Sodium-Potassium-Exchanging ATPase
Thiobarbituric Acid Reactive Substances

Substances

Peptides
Thiobarbituric Acid Reactive Substances
Nitric Oxide
N-Methylaspartate
Dizocilpine Maleate
Sodium-Potassium-Exchanging ATPase
Cyclic GMP
NG-Nitroarginine Methyl Ester