Na+,K+-ATPase As a Polyfunctional Protein

IF 1.1 Q4 CELL BIOLOGY

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2022-08-15 DOI:10.1134/S1990747822040055

O. D. Lopina, O. V. Bukach, S. V. Sidorenko, E. A. Klimanova

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引用次数: 0

Abstract—

Since the discovery of Na⁺,K⁺-ATPase by Jens Skou in 1957, this enzyme has been considered exclusively as a transporter that ensures the active transport of Na⁺ and K⁺ ions across the cell plasma membrane; therefore, its structure and mechanism of functioning, as well as its involvement in secondary ion transport systems have been studied in detail. In the present review, the data on the structure and functioning of the enzyme are briefly reviewed. The role of Na⁺,K⁺-ATPase as a receptor for cardiotonic steroids (CTS), whose binding to the enzyme initiates a variety of signaling pathways through protein–protein interactions modified also by changes in the intracellular concentration of Na⁺ and K⁺ ions by inhibiting the Na⁺,K⁺-ATPase transport function and Ca²⁺, by mediating changes in Na/Ca-exchange activity, was described in more detail. All these provide a variety of CTS effects, including their effect on gene expression, the state of tight junctions, cell adhesion, induction of myocardial hypertrophy, stimulation of free-radical oxygen species generation, and initiation of cell death or survival depending on tissue type. Data on the discovery of endogenous CTS are presented, as well as an analysis of published data indicating that concentrations of endogenous CTS are so low that they are unlikely to cause inhibition of Na⁺,K⁺-ATPase. In this connection, the data on the enzyme activation by low doses of CTS are presented, and the idea of a possible summation of the concentrations of various steroids is suggested. Possible directions for the study of multiple functions of Na⁺,K⁺-ATPase are discussed in the conclusion.

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Na+，K+- atp酶作为一种多功能蛋白

自1957年Jens Skou发现Na+，K+- atp酶以来，这种酶一直被认为是一种确保Na+和K+离子在细胞质膜上主动运输的转运体;因此，对其结构、作用机制及其在二次离子输运系统中的作用进行了详细的研究。本文就该酶的结构和功能方面的研究进展作一综述。Na+，K+- atp酶作为强心性类固醇(CTS)的受体，其与酶的结合通过蛋白-蛋白相互作用启动了多种信号通路，通过抑制Na+，K+- atp酶转运功能和Ca2+，通过介导Na/ ca交换活性的变化，细胞内Na+和K+离子浓度的变化也改变了信号通路。所有这些都提供了多种CTS效应，包括其对基因表达、紧密连接状态、细胞粘附、诱导心肌肥大、刺激自由基氧的产生以及根据组织类型启动细胞死亡或存活的影响。本文介绍了内源性CTS的发现数据，并对已发表的数据进行了分析，表明内源性CTS的浓度很低，不太可能引起Na+，K+- atp酶的抑制。在这方面，提出了低剂量CTS对酶活化的数据，并提出了各种类固醇浓度可能的总和的想法。最后讨论了Na+，K+- atp酶多种功能研究的可能方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology CELL BIOLOGY-

CiteScore

1.40

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.