Understanding the mechanism involved in lung epithelial potassium current modulation by ozone

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2025-06-27 DOI:10.1016/j.abb.2025.110522

Rita Canella , Mascia Benedusi , Giulia Trinchera , Angela Pignatelli , Giuseppe Valacchi

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引用次数: 0

Abstract

Given that the ionic balance of the pulmonary alveolar lining fluid is essential for correct gas exchange, our previous studies analyzed the effects of ozone (O₃), one of the most harmful pollutants for the respiratory system, on K⁺ current (I_K)in human cultured lung epithelial cells (A549). O₃ exposure significantly alters the flow of K⁺ ions, reducing the outward rectifier current component. O₃ does not act directly, but through its byproducts, among which the main ones are 4-hydroxy-2-nonenal (4HNE) and hydrogen peroxide (H₂O₂).

In this study we analyzed the action of 4HNE and H₂O₂ on I_K in human lung cells and verified the protective effect of catalase.

Material

A549 cellular line. 30’ exposure: O₃: 0.1 ppm; 4HNE: 5, 10 and 20 μM; H₂O₂: 20 μM. Glucose-oxidase: 10 mU/l, 1.00h exposure, analyzed after 24h. Catalase: 1000 U, 1.30h exposure.

Methods

Western blot, immunofluorescence and patch clamp techniques to study the action of the bio-products on I_K.

4HNE was able to significantly decrease the I_K, but it was less effective than O₃. H₂O₂ produced by the cells after GO administration completely reproduced the O₃ effect. Catalase showed its ability in preserving the outward rectifier component depressed by O₃, bringing back the current to the control level.

We can conclude that 4HNE and H₂O₂ are responsible for the O₃ action on potassium channels. The protective role of catalase confirms the ability of O₃ bio-product to modify the cellular redox homeostasis. In perspective it will be interesting to analyze their interaction, and the bio-molecular pathways activated.

Abstract Image

查看原文本刊更多论文

了解臭氧对肺上皮钾电流调节的机制。

鉴于肺泡衬液的离子平衡对正确的气体交换至关重要，我们之前的研究分析了臭氧（O3）对人类培养的肺上皮细胞（A549）中K+电流（IK）的影响，臭氧是呼吸系统最有害的污染物之一。O3暴露显著改变了K+离子的流动，减小了向外整流电流分量。O3不是直接作用，而是通过它的副产物，其中主要是4-羟基-2-壬烯醛（4HNE）和过氧化氢（H2O2）。本研究分析了4HNE和H2O2对人肺细胞IK的作用，验证了过氧化氢酶的保护作用。材料：A549蜂窝细胞系。30'曝光：O3: 0.1 ppm；4HNE: 5, 10和20微米；H2O2: 20um。葡萄糖氧化酶：10 mU/l，暴露1.00h， 24h后分析。过氧化氢酶：1000U，暴露1.30h。方法：采用Western blot、免疫荧光和膜片钳技术研究生物制品对IK的作用。4HNE能显著降低IK，但效果不如O3。氧化石墨烯给药后细胞产生的H2O2完全再现了O3效应。过氧化氢酶表现出保留被O3抑制的外向整流组分的能力，使电流恢复到控制水平。我们可以得出结论，4HNE和H2O2负责O3对钾通道的作用。过氧化氢酶的保护作用证实了O3生物产物改变细胞氧化还原稳态的能力。从长远来看，分析它们的相互作用和激活的生物分子途径将是有趣的。

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.