Dabrowska 2023 Int J Mol Sci
| Dabrowska A, Zajac M, Bednarczyk P, Lukasiak A (2023) Effect of quercetin on mitoBKCa channel and mitochondrial function in human bronchial epithelial cells exposed to particulate matter. Int J Mol Sci 24:638. https://doi.org/10.3390/ijms24010638 |
Dabrowska Adrianna, Zajac Miroslaw, Bednarczyk Piotr, Lukasiak Agnieszka (2023) Int J Mol Sci
Abstract: Particulate matter (PM) exposure increases reactive oxygen species (ROS) levels. It can lead to inflammatory responses and damage of the mitochondria thus inducing cell death. Recently, it has been shown that potassium channels (mitoK) located in the inner mitochondrial membrane are involved in cytoprotection, and one of the mechanisms involves ROS. To verify the cytoprotective role of mitoBKCa, we performed a series of experiments using a patch-clamp, transepithelial electrical resistance assessment (TEER), mitochondrial respiration measurements, fluorescence methods for the ROS level and mitochondrial membrane potential assessment, and cell viability measurements. In the human bronchial epithelial cell model (16HBE14Ο), PM < 4 ΞΌm in diameter (SRM-PM4.0) was used. We observed that PM decreased TEER of HBE cell monolayers. The effect was partially abolished by quercetin, a mitoBKCa opener. Consequently, quercetin decreased the mitochondrial membrane potential and increased mitochondrial respiration. The reduction of PM-induced ROS level occurs both on cellular and mitochondrial level. Additionally, quercetin restores HBE cell viability after PM administration. The incubation of cells with PM substantially reduced the mitochondrial function. Isorhamnetin had no effect on TEER, the mitoBKCa activity, respiratory rate, or mitochondrial membrane potential. Obtained results indicate that PM has an adverse effect on HBE cells at the cellular and mitochondrial level. Quercetin is able to limit the deleterious effect of PM on barrier function of airway epithelial cells. We show that the effect in HBE cells involves mitoBKCa channel-activation. However, quercetinβs mechanism of action is not exclusively determined by modulation of the channel activity. β’ Keywords: Epithelium, mitoBKCa channel, Mitochondria, Particulate matter, Quercetin β’ Bioblast editor: Plangger M β’ O2k-Network Lab: PL Warsaw Bednarczyk P
Labels: MiParea: Respiration, mt-Membrane, Pharmacology;toxicology
Stress:Oxidative stress;RONS Organism: Human Tissue;cell: Lung;gill, Endothelial;epithelial;mesothelial cell Preparation: Permeabilized cells, Intact cells
Regulation: Ion;substrate transport, mt-Membrane potential Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: S, ROX HRR: Oxygraph-2k, O2k-Fluorometer
2024-03
