Journal
CELLS
Volume 11, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/cells11172753
Keywords
Na; K-ATPase; beta-amyloid; Src kinase; hypoxia; receptor function
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Funding
- Russian Science Foundation [19-74-30007]
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This study reveals that Na,K-ATPase serves as a receptor for Aβ(42), triggering Src kinase activation. This finding provides insights into the physiological and pathological Src kinase activation caused by Aβ(42) in the nervous system.
Beta-amyloid (A beta) 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 A beta(42) oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer's disease. Still, the physiological role of the monomeric form of A beta(42) interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for A beta(42) monomer, triggering Src kinase activation. The co-localization of A beta(42) with alpha 1- and beta 1-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 A beta(42) causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of A beta(42) with alpha 1 beta 1 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 A beta-induced Src kinase activation. Stimulatory effect of A beta(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 A beta(42) receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by A beta(42) in the nervous system.
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