Academic Journal
Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation
| العنوان: | Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation |
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| المؤلفون: | 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 |
| المصدر: | 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 (2022). Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation. Cells, 11(17):2753. |
| بيانات النشر: | MDPI Publishing |
| سنة النشر: | 2022 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Zurich Center for Integrative Human Physiology (ZIHP), Institute of Veterinary Physiology, 570 Life sciences, biology, General Medicine |
| الوصف: | 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 Aβ42 oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the monomeric form of Aβ42 interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ42 monomer, triggering Src kinase activation. The co-localization of Aβ42 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 Aβ42 causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ42 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 Aβ42 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 Aβ42 receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ42 in the nervous system. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| Relation: | https://www.zora.uzh.ch/id/eprint/231081/1/ZORA_pdf_version_1662204547.pdf; info:pmid/36078160; urn:issn:2073-4409 |
| DOI: | 10.3390/cells11172753 |
| الاتاحة: | https://www.zora.uzh.ch/id/eprint/231081/ https://www.zora.uzh.ch/id/eprint/231081/1/ZORA_pdf_version_1662204547.pdf https://doi.org/10.3390/cells11172753 |
| Rights: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.3C8F6191 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20734409 |
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| DOI: | 10.3390/cells11172753 |