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Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation
Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer’s disease and as a regulator in brain physiology. The inhibitory effect of Aβ(42) oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the mon...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455167/ https://www.ncbi.nlm.nih.gov/pubmed/36078160 http://dx.doi.org/10.3390/cells11172753 |
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author | Petrushanko, Irina Yu. Tverskoi, Artem M. Barykin, Evgeny P. Petrovskaya, Aleksandra V. Strelkova, Maria A. Leonova, Olga G. Anashkina, Anastasia A. Tolstova, Anna P. Adzhubei, Alexei A. Bogdanova, Anna Yu. Makarov, Alexander A. Mitkevich, Vladimir A. |
author_facet | Petrushanko, Irina Yu. Tverskoi, Artem M. Barykin, Evgeny P. Petrovskaya, Aleksandra V. Strelkova, Maria A. Leonova, Olga G. Anashkina, Anastasia A. Tolstova, Anna P. Adzhubei, Alexei A. Bogdanova, Anna Yu. Makarov, Alexander A. Mitkevich, Vladimir A. |
author_sort | Petrushanko, Irina Yu. |
collection | PubMed |
description | Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer’s disease and as a regulator in brain physiology. The inhibitory effect of Aβ(42) oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the monomeric form of Aβ(42) interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ(42) monomer, triggering Src kinase activation. The co-localization of Aβ(42) with α1- and β1-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM Aβ(42) causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ(42) with α1β1 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the Aβ-induced Src kinase activation. Stimulatory effect of Aβ(42) on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a Aβ(42) receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ(42) in the nervous system. |
format | Online Article Text |
id | pubmed-9455167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94551672022-09-09 Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation Petrushanko, Irina Yu. Tverskoi, Artem M. Barykin, Evgeny P. Petrovskaya, Aleksandra V. Strelkova, Maria A. Leonova, Olga G. Anashkina, Anastasia A. Tolstova, Anna P. Adzhubei, Alexei A. Bogdanova, Anna Yu. Makarov, Alexander A. Mitkevich, Vladimir A. Cells Article Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer’s disease and as a regulator in brain physiology. The inhibitory effect of Aβ(42) oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the monomeric form of Aβ(42) interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ(42) monomer, triggering Src kinase activation. The co-localization of Aβ(42) with α1- and β1-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM Aβ(42) causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ(42) with α1β1 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the Aβ-induced Src kinase activation. Stimulatory effect of Aβ(42) on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a Aβ(42) receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ(42) in the nervous system. MDPI 2022-09-03 /pmc/articles/PMC9455167/ /pubmed/36078160 http://dx.doi.org/10.3390/cells11172753 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Petrushanko, Irina Yu. Tverskoi, Artem M. Barykin, Evgeny P. Petrovskaya, Aleksandra V. Strelkova, Maria A. Leonova, Olga G. Anashkina, Anastasia A. Tolstova, Anna P. Adzhubei, Alexei A. Bogdanova, Anna Yu. Makarov, Alexander A. Mitkevich, Vladimir A. Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title_full | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title_fullStr | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title_full_unstemmed | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title_short | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
title_sort | na,k-atpase acts as a beta-amyloid receptor triggering src kinase activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455167/ https://www.ncbi.nlm.nih.gov/pubmed/36078160 http://dx.doi.org/10.3390/cells11172753 |
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