Cumhur Cure Medine, Cure Erkan
Department of Biochemistry, Private Kucukcekmece Hospital, Istanbul, Turkey.
Department of Internal Medicine, Ota&Jinemed Hospital, Istanbul, Turkey.
J Renin Angiotensin Aldosterone Syst. 2021 Jun 15;2021:4754440. doi: 10.1155/2021/4754440. eCollection 2021.
The Na/H ion exchanger (NHE) pumps Na inward the cell and H ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.
钠/氢离子交换器（NHE）将钠离子泵入细胞内，同时将氢离子泵出细胞外。NHE的活性会随着细胞内pH值的降低而增加，并将细胞内pH值维持在一个狭窄的范围内。肥胖、糖尿病、高血压患者以及老年人更容易感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。在糖尿病、高血压和肥胖等慢性疾病中，血管紧张素II（Ang II）水平较高。Ang II是NHE的主要刺激物，Ang II水平升高会导致这些患者的NHE持续激活。在糖尿病、高血压和肥胖患者中，NHE活性的长期增加会导致氢离子离开细胞。细胞外氢离子增加会导致氧化应激和活性氧增加。由于氧化应激增加，氢离子会流入细胞。这种恶性循环会导致细胞内pH值下降。虽然细胞内pH值降低时NHE会被激活，但在上述慢性疾病中NHE会持续激活。在这些患者中，2019冠状病毒病（COVID-19）的病情可能会更严重，死亡率更高。SARS-CoV-2在低细胞内pH值时很容易侵入细胞并引发感染。肾素-血管紧张素系统和NHE在调节细胞内pH值方面起着至关重要的作用。NHE活性降低或其持续激活可能会通过降低糖尿病、高血压和肥胖患者的细胞内pH值而导致对SARS-CoV-2感染的易感性。这些COVID-19患者中NHE的持续激活可能会使病情恶化。科学家们继续研究该疾病的发病机制以及影响其临床进展的因素。
