Cordeiro Bárbara Martins, Leite Fontes Carlos Frederico, Meyer-Fernandes José Roberto
Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil.
Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro 21941-590, RJ, Brazil.
Int J Mol Sci. 2024 Dec 13;25(24):13398. doi: 10.3390/ijms252413398.
The Na, K-ATPase generates an asymmetric ion gradient that supports multiple cellular functions, including the control of cellular volume, neuronal excitability, secondary ionic transport, and the movement of molecules like amino acids and glucose. The intracellular and extracellular levels of Na and K ions are the classical local regulators of the enzyme's activity. Additionally, the regulation of Na, K-ATPase is a complex process that occurs at multiple levels, encompassing its total cellular content, subcellular distribution, and intrinsic activity. In this context, the enzyme serves as a regulatory target for hormones, either through direct actions or via signaling cascades triggered by hormone receptors. Notably, FXYDs small transmembrane proteins regulators of Na, K-ATPase serve as intermediaries linking hormonal signaling to enzymatic regulation at various levels. Specifically, members of the FXYD family, particularly FXYD1 and FXYD2, are that undergo phosphorylation by kinases activated through hormone receptor signaling, which subsequently influences their modulation of Na, K-ATPase activity. This review describes the effects of FXYD2, cardiotonic steroid signaling, and hormones such as angiotensin II, dopamine, insulin, and catecholamines on the regulation of Na, K-ATPase. Furthermore, this review highlights the implications of Na, K-ATPase in diseases such as hypertension, renal hypomagnesemia, and cancer.
钠钾ATP酶产生一种不对称离子梯度，该梯度支持多种细胞功能，包括细胞体积控制、神经元兴奋性、继发性离子转运以及氨基酸和葡萄糖等分子的移动。钠和钾离子的细胞内和细胞外水平是该酶活性的经典局部调节因子。此外，钠钾ATP酶的调节是一个复杂的过程，发生在多个层面，包括其细胞总含量、亚细胞分布和内在活性。在这种情况下，该酶作为激素的调节靶点，要么通过直接作用，要么通过激素受体触发的信号级联反应。值得注意的是，FXYD家族的小跨膜蛋白作为钠钾ATP酶的调节因子，在各个层面上充当将激素信号与酶调节联系起来的中介。具体而言，FXYD家族成员，特别是FXYD1和FXYD2，会被通过激素受体信号激活的激酶磷酸化，这随后会影响它们对钠钾ATP酶活性的调节。本综述描述了FXYD2、强心甾类信号以及血管紧张素II、多巴胺、胰岛素和儿茶酚胺等激素对钠钾ATP酶调节的影响。此外，本综述强调了钠钾ATP酶在高血压、肾性低镁血症和癌症等疾病中的意义。
