Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA; Hypertension and Kidney Research Center, University of South Florida, Tampa, Florida, USA.
J Biol Chem. 2024 Oct;300(10):107781. doi: 10.1016/j.jbc.2024.107781. Epub 2024 Sep 12.
Zinc is one of the essential divalent cations in the human body and a fundamental microelement involved in the regulation of many cellular and subcellular functions. Experimental studies reported that zinc deficiency is associated with renal damage and could increase blood pressure. It was proposed that zinc dietary supplementation plays a renoprotective role. Our study aimed to investigate the effects of zinc on intracellular signaling in renal cells and explore the correlation between dietary zinc and the progression of salt-induced hypertension. The impact of extracellular zinc concentrations on two different kidney epithelial cell types, podocytes and principal cells of the cortical collecting duct (CCD), was tested. In podocytes, a rise in extracellular zinc promotes TRPC6 channel-mediated calcium entry but not altered intracellular zinc levels. However, we observe the opposite effect in CCD cells with no alteration in calcium levels and steady-state elevation in intracellular zinc. Moreover, prolonged extracellular zinc exposure leads to cytotoxic insults in CCD cells but not in podocytes, characterized by increased cell death and disrupted cytoskeletal organization. Next, we tested if dietary zinc plays a role in the development of hypertension in Dahl salt-sensitive rats. Neither zinc-rich nor deficient diets impact the regular development of salt-sensitive hypertension. These results suggest specialized roles for zinc in renal function, implicating its involvement in proliferation and apoptosis in CCD cells and calcium signaling and cytoskeletal dynamics modulation in podocytes. Further research is required to elucidate the detailed mechanisms of zinc action and its implications in renal health and disease.
锌是人体必需的二价阳离子之一，也是调节许多细胞和亚细胞功能的基本微量元素。实验研究表明，锌缺乏与肾脏损伤有关，并可能导致血压升高。有研究提出，锌的膳食补充具有肾脏保护作用。本研究旨在探讨锌对肾脏细胞内信号转导的影响，并探讨膳食锌与盐诱导高血压进展之间的相关性。研究测试了细胞外锌浓度对两种不同的肾脏上皮细胞类型（足细胞和皮质集合管主细胞）的影响。在足细胞中，细胞外锌的增加促进了 TRPC6 通道介导的钙内流，但不会改变细胞内锌水平。然而，在 CCD 细胞中观察到相反的效果，钙水平没有改变，细胞内锌水平稳定升高。此外，延长细胞外锌暴露会导致 CCD 细胞发生细胞毒性损伤，但不会导致足细胞发生这种损伤，其特征是细胞死亡增加和细胞骨架组织紊乱。接下来，我们测试了膳食锌是否在 Dahl 盐敏感大鼠高血压的发展中起作用。富含锌和缺锌的饮食均不会影响盐敏感高血压的正常发展。这些结果表明锌在肾脏功能中具有特殊作用，提示其参与 CCD 细胞的增殖和凋亡，以及足细胞的钙信号和细胞骨架动力学调节。需要进一步研究来阐明锌作用的详细机制及其在肾脏健康和疾病中的意义。
