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

Author(s)

Kawamoto, E. M. ^[1] ; Cararo-Lopes, M. M. ^[2] ; Kinoshita, P. F. ^[2] ; Quintas, L. E. M. ^[3] ; Lima, L. S. ^[2] ; Andreotti, D. Z. ^{[1, 2]} ; Scavone, C. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Mol & Funct Neurobiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Mol Neuropharmacol, Sao Paulo - Brazil

^[3] Fed Univ Rio de Janeiro UFRJ, Inst Biomed Sci, Lab Biochem & Mol Pharmacol, Hlth Sci Ctr, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: Journal of Membrane Biology; v. 254, n. 5-6, SI JUL 2021.
• Web of Science Citations: 1

Abstract

Amyloid-beta peptide (A beta) 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 A beta in relation to NMDA-NOS-cyclic GMP versus oxidative stress on alpha(1)-/alpha(2,3)-Na,K-ATPase activities in rat hippocampal slices. A beta(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 A beta(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 A beta 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 A beta was isoform-specific since only alpha(1)-Na,K-ATPase was affected. These findings suggest that the activation of NMDA-NOS signaling cascade linked to alpha(2,3)-Na,K-ATPase activity may mediate an adaptive, neuroprotective response to A beta in rat hippocampus. (AU)

• FAPESP's process: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system
• Grantee: Cristoforo Scavone
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/22996-9 - Evaluation of physical exercise effects on cognition of neuronal-PTEN deleted animals
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/14289-6 - The role of Klotho protein in Alzheimer's disease
• Grantee: Paula Fernanda Kinoshita
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/12974-6 - Evaluation of PTEN inhibition and compartmentalization effects in the presence of neuroinflammation: participation of glutamatergic signaling
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/14199-6 - Modulation of Na, K-ATPase through cyclic GMP and nitric oxide pathway in central nervous system of Klotho knockout mice
• Grantee: Marina Minto Cararo Lopes
• Support Opportunities: Scholarships in Brazil - Master