Modulation of the Respiratory Epithelium Physiology by Flavonoids-Insights from 16HBEσcell Model.

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used for centuries to prevent and treat numerous ailments. Lately, a growing body of evidence suggests that flavonoids can enhance the integrity of the airway epithelial barrier.

Anticancer activity of salinomycin quaternary phosphonium salts.

In recent years salinomycin has emerged as a promising anticancer drug. Many literature reports have proved its remarkable antiproliferative activity. Moreover, chemical modifications of salinomycin lead to analogues with even higher cytotoxicity against cancer cell lines and a better selectivity index for malignant cells than those of the unmodified compound or a standard anticancer drug such as doxorubicin.

mitoBK is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming.

Alterations in the function of K channels such as the voltage- and Ca-activated K channel of large conductance (BK) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK).

Deficiency of the BK potassium channel displayed significant implications for the physiology of the human bronchial epithelium.

Plasma membrane large-conductance calcium-activated potassium (BK) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epithelial (HBE) cells also express BK in the inner mitochondrial membrane (mitoBK). The genetic relationships between these mitochondrial and plasma membrane channels and the precise role of mitoBK in epithelium physiology are still unclear.

Novel insights into the role of ion channels in cellular DNA damage response.

The DNA damage response (DDR) is a complex and highly regulated cellular process that detects and repairs DNA damage. The integrity of the DNA molecule is crucial for the proper functioning and survival of cells, as DNA damage can lead to mutations, genomic instability, and various diseases, including cancer. The DDR safeguards the genome by coordinating a series of signaling events and repair mechanisms to maintain genomic stability and prevent the propagation of damaged DNA to daughter cells.

Changes in Ion Transport across Biological Membranes Exposed to Particulate Matter.

The cells of living organisms are surrounded by the biological membranes that form a barrier between the internal and external environment of the cells. Cell membranes serve as barriers and gatekeepers. They protect cells against the entry of undesirable substances and are the first line of interaction with foreign particles.

Lack of activity of the mitochondrial large-conductance calcium-regulated potassium channels in senescent vascular smooth muscle cells.

A limited number of studies have shown functional changes in mitochondrial ion channels in aging and senescent cells. We have identified, for the first time, mitochondrial large-conductance calcium-regulated potassium channels in human smooth muscle mitochondria. This channel, with a conductance of 273 pS, was regulated by calcium ions and membrane potential.

Membrane lytic activity of antibacterial ionenes, critical role of phosphatidylcholine (PC) and cardiolipin (CL).

Understanding the mechanism by which an antibacterial agent interacts with a model membrane provides vital information for better design of future antibiotics. In this study, we investigated two antibacterial polymers, hydrophilic C0-T-p and hydrophobic C8-T-p ionenes, known for their potent antimicrobial activity and ability to disrupt the integrity of lipid bilayers. Our hypothesize is that the composition of a lipid bilayer alters the mechanism of ionenes action, potentially providing an explanation for the observed differences in their bioactivity and selectivity.

Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells.

Mitochondrial potassium (mitoK) channels play an important role in cellular physiology. These channels are expressed in healthy tissues and cancer cells. Activation of mitoK channels can protect neurons and cardiac tissue against injury induced by ischemia-reperfusion.

The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids.

The activity of mitochondrial large-conductance voltage- and [Formula: see text]-activated [Formula: see text] channels (mitoBK) is regulated by a number of biochemical factors, including flavonoids. In particular, naringenin (Nar) and quercetin (Que) reached reasonable scientific attention due to their well-pronounced channel-activating effects. The open-reinforcing outcomes of Nar and Que on the mitoBK channel gating have been already reported.

Electrochemical studies of the mitochondrial ROMK2 potassium channel activity reconstituted into the free-standing and tethered bilayer lipid membranes.

The renal-outer-medullary‑potassium (ROMK2) channel modulates potassium transport in the kidney. It has been postulated that the ROMK2 is the pore-forming subunit of the mitochondrial ATP-sensitive potassium channel as a mediator of cardioprotection. In this study, cell-free synthesis of the ROMK2 was performed in presence of membrane scaffold protein (MSP1D1) nanodiscs.

Effect of Quercetin on mitoBK Channel and Mitochondrial Function in Human Bronchial Epithelial Cells Exposed to Particulate Matter.

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.

Flavonoids as new regulators of mitochondrial potassium channels: contribution to cardioprotection.

Objectives: Acute myocardial ischemia is one of the major causes of illness in western society. Reduced coronary blood supply leads to cell death and loss of cardiomyocyte population, resulting in serious and often irreversible consequences on myocardial function. Mitochondrial potassium (mitoK) channels have been identified as fine regulators of mitochondrial function and, consequently, in the metabolism of the whole cell, and in the mechanisms underlying the cardioprotection.

Luteolin-Induced Activation of Mitochondrial BK Channels: Undisclosed Mechanism of Cytoprotection.

Luteolin (LUT) is a well-known flavonoid that exhibits a number of beneficial properties. Among these, it shows cardioprotective effects, as confirmed by numerous studies. However, its effect on mitochondrial potassium channels, the activation of which is related to cytoprotection, as well as on heart ischemia/reperfusion (I/R) damage prevention, has not yet been investigated.

To what extent naringenin binding and membrane depolarization shape mitoBK channel gating-A machine learning approach.

The large conductance voltage- and Ca2+-activated K+ channels from the inner mitochondrial membrane (mitoBK) are modulated by a number of factors. Among them flavanones, including naringenin (Nar), arise as a promising group of mitoBK channel regulators from a pharmacological point of view. It is well known that in the presence of Nar the open state probability (pop) of mitoBK channels significantly increases.

New Diagnostic Tool for Ion Channel Activity Hidden Behind the Dwell-Time Correlations.

The patch-clamp technique is a powerful tool that allows for a long observation of transport protein activity in real time. Experimental traces of single-channel currents can be considered as a record of the channel's conformational switching related to its activation and gating. In this work, we present a mathematically simple method of patch-clamp data analysis that assesses the connectivity and occupancy of distinct conformational substates of the channel.

Flavonoid quercetin abolish paxilline inhibition of the mitochondrial BK channel.

Large-conductance calcium-regulated potassium channel (BK) is known to play an important role in physiological and pathological processes. Despite the BK channel being encoded by one gene, this channel has been found to be located not only in the cell membrane but also in the membranes of intracellular compartments, such as in the inner mitochondrial membrane. With some differences, the mitochondrial BK (mitoBK) channel has been shown to be activated or inhibited by both synthetic and natural compounds.

Methods of Measuring Mitochondrial Potassium Channels: A Critical Assessment.

In this paper, the techniques used to study the function of mitochondrial potassium channels are critically reviewed. The majority of these techniques have been known for many years as a result of research on plasma membrane ion channels. Hence, in this review, we focus on the critical evaluation of techniques used in the studies of mitochondrial potassium channels, describing their advantages and limitations.

Cytoprotective effects of the flavonoid quercetin by activating mitochondrial BK channels in endothelial cells.

Mitochondrial potassium channels have been implicated in cytoprotective mechanisms. Activation of the mitochondrial large-conductance Ca-regulated potassium (mitoBK) channel is important for protecting brain tissue against stroke damage as well as heart tissue against ischemia damage. In this paper, we examine the effect of the natural flavonoid quercetin as an activator of the mitoBK channel.

Prompt-gamma emission in GEANT4 revisited and confronted with experiment.

Purpose: The field of online monitoring of the beam range is one of the most researched topics in proton therapy over the last decade. The development of detectors that can be used for beam range verification under clinical conditions is a challenging task. One promising possible solution are modalities that record prompt-gamma radiation produced by the interactions of the proton beam with the target tissue.

Multidimensional Regulation of Cardiac Mitochondrial Potassium Channels.

Mitochondria play a fundamental role in the energetics of cardiac cells. Moreover, mitochondria are involved in cardiac ischemia/reperfusion injury by opening the mitochondrial permeability transition pore which is the major cause of cell death. The preservation of mitochondrial function is an essential component of the cardioprotective mechanism.

Identification of the Large-Conductance Ca-Regulated Potassium Channel in Mitochondria of Human Bronchial Epithelial Cells.

Mitochondria play a key role in energy metabolism within the cell. Potassium channels such as ATP-sensitive, voltage-gated or large-conductance Ca-regulated channels have been described in the inner mitochondrial membrane. Several hypotheses have been proposed to describe the important roles of mitochondrial potassium channels in cell survival and death pathways.