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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 |
Sumario: | 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. |
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