Research

Jump to: Review

11 pages, 2006 KiB

Open AccessArticle

Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening

by Tatiana Fedotcheva, Nikolai Shimanovsky and Nadezhda Fedotcheva

Membranes 2023, 13(4), 372; https://doi.org/10.3390/membranes13040372 - 24 Mar 2023

Cited by 3 | Viewed by 1341

Abstract

Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferroptosis-type cell death. We investigated the effect of TBH on the [...] Read more.

Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferroptosis-type cell death. We investigated the effect of TBH on the induction of nonspecific membrane permeability measured by mitochondrial swelling and on oxidative phosphorylation and NADH oxidation assessed by NADH fluo rescence. TBH and iron, as well as their combinations, induced, with a respective decrease in the lag phase, the swelling of mitochondria, inhibited oxidative phosphorylation and stimulated NADH oxidation. The lipid radical scavenger butylhydroxytoluene (BHT), the inhibitor of mitochondrial phospholipase iPLA2γ bromoenol lactone (BEL), and the inhibitor of the mitochondrial permeability transition pore (MPTP) opening cyclosporine A (CsA) were equally effective in protecting these mitochondrial functions. The radical-trapping antioxidant ferrostatin-1, a known indicator of ferroptotic alteration, restricted the swelling but was less effective than BHT. ADP and oligomycin significantly decelerated iron- and TBH-induced swelling, confirming the involvement of MPTP opening in mitochondrial dysfunction. Thus, our data showed the participation of phospholipase activation, lipid peroxidation, and the MPTP opening in the mitochondria-dependent ferroptosis. Presumably, their involvement took place at different stages of membrane damage initiated by ferroptotic stimuli. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

17 pages, 2535 KiB

Open AccessArticle

Modified Signaling of Membrane Formyl Peptide Receptors in NADPH-Oxidase Regulation in Obesity-Resistant Mice

by Irina Tikhonova, Alsu Dyukina, Elvira Shaykhutdinova and Valentina Safronova

Membranes 2023, 13(3), 306; https://doi.org/10.3390/membranes13030306 - 06 Mar 2023

Cited by 1 | Viewed by 1121

Abstract

The signaling of membrane receptors is modified in obesity characterized by low-grade inflammation. The obesity-resistant state of organisms is poorly understood. We analyzed the generation of reactive oxygen species (ROS) initiated though membrane formyl peptide receptors (Fpr1, Fpr2) in bone-marrow granulocytes of obesity-resistant [...] Read more.

The signaling of membrane receptors is modified in obesity characterized by low-grade inflammation. The obesity-resistant state of organisms is poorly understood. We analyzed the generation of reactive oxygen species (ROS) initiated though membrane formyl peptide receptors (Fpr1, Fpr2) in bone-marrow granulocytes of obesity-resistant mice (ORM). A chemiluminescence assay was used to assess NADPH-oxidase-related intensity of ROS generation. ORM were chosen from animals that received high-fat diets and had metric body parameters as controls (standard diet). High spontaneous ROS production was observed in ORM cells. The EC50 for responses to bacterial or mitochondrial peptide N-formyl-MLF was higher in ORM with and without inflammation vs. the same control groups, indicating an insignificant role of high-affinity Fpr1. Increased responses to synthetic peptide WKYMVM (Fpr2 agonist) were observed in controls with acute inflammation, but they were similar in other groups. Fpr2 was possibly partially inactivated in ORM owing to the inflammatory state. Weakened Fpr1 and Fpr2 signaling via MAPKs was revealed in ORM using specific inhibitors for p38, ERK1/2, and JNK. P38 signaling via Fpr2 was lower in ORM with inflammation. Thus, a high-fat diet modified FPRs’ role and suppressed MAPK signaling in NADPH-oxidase regulation in ORM. This result can be useful to understand the immunological features of obesity resistance. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Graphical abstract

11 pages, 1946 KiB

Open AccessArticle

The Infarct-Reducing Effect of the δ₂ Opioid Receptor Agonist Deltorphin II: The Molecular Mechanism

by Sergey V. Popov, Alexandr V. Mukhomedzyanov, Leonid N. Maslov, Natalia V. Naryzhnaya, Boris K. Kurbatov, N. Rajendra Prasad, Nirmal Singh, Feng Fu and Viacheslav N. Azev

Membranes 2023, 13(1), 63; https://doi.org/10.3390/membranes13010063 - 04 Jan 2023

Cited by 3 | Viewed by 2010

Abstract

The search for novel drugs for the treatment of acute myocardial infarction and reperfusion injury of the heart is an urgent aim of modern pharmacology. Opioid peptides could be such potential drugs in this area. However, the molecular mechanism of the infarct-limiting effect [...] Read more.

The search for novel drugs for the treatment of acute myocardial infarction and reperfusion injury of the heart is an urgent aim of modern pharmacology. Opioid peptides could be such potential drugs in this area. However, the molecular mechanism of the infarct-limiting effect of opioids in reperfusion remains unexplored. The objective of this research was to study the signaling mechanisms of the cardioprotective effect of deltorphin II in reperfusion. Rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). The ratio of infarct size/area at risk was determined. This study indicated that the cardioprotective effect of deltorphin II in reperfusion is mediated via the activation of peripheral δ₂ opioid receptor (OR), which is most likely localized in cardiomyocytes. We studied the role of guanylyl cyclase, protein kinase Cδ (PKCδ), phosphatidylinositol-3-kinase (PI3-kinase), extracellular signal-regulated kinase-1/2 (ERK1/2-kinase), ATP-sensitive K⁺-channels (K_ATP channels), mitochondrial permeability transition pore (MPTP), NO synthase (NOS), protein kinase A (PKA), Janus 2 kinase, AMP-activated protein kinase (AMPK), the large conductance calcium-activated potassium channel (BK_Ca-channel), reactive oxygen species (ROS) in the cardioprotective effect of deltorphin II. The infarct-reducing effect of deltorphin II appeared to be mediated via the activation of PKCδ, PI3-kinase, ERK1/2-kinase, sarcolemmal K_ATP channel opening, and MPTP closing. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

29 pages, 5493 KiB

Open AccessArticle

Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers

by Alexey S. Averin, Maxim V. Konakov, Oleg Y. Pimenov, Miliausha H. Galimova, Alexey V. Berezhnov, Miroslav N. Nenov and Vladimir V. Dynnik

Membranes 2022, 12(12), 1239; https://doi.org/10.3390/membranes12121239 - 07 Dec 2022

Cited by 1 | Viewed by 1801

Abstract

Various models, including stem cells derived and isolated cardiomyocytes with overexpressed channels, are utilized to analyze the functional interplay of diverse ion currents involved in cardiac automaticity and excitation–contraction coupling control. Here, we used β-NAD and ammonia, known hyperpolarizing and depolarizing agents, respectively, [...] Read more.

Various models, including stem cells derived and isolated cardiomyocytes with overexpressed channels, are utilized to analyze the functional interplay of diverse ion currents involved in cardiac automaticity and excitation–contraction coupling control. Here, we used β-NAD and ammonia, known hyperpolarizing and depolarizing agents, respectively, and applied inhibitory analysis to reveal the interplay of several ion channels implicated in rat papillary muscle contractility control. We demonstrated that: 4 mM β-NAD, having no strong impact on resting membrane potential (RMP) and action potential duration (APD90) of ventricular cardiomyocytes, evoked significant suppression of isometric force (F) of paced papillary muscle. Reactive blue 2 restored F to control values, suggesting the involvement of P2Y-receptor-dependent signaling in β-NAD effects. Meantime, 5 mM NH₄Cl did not show any effect on F of papillary muscle but resulted in significant RMP depolarization, APD90 shortening, and a rightward shift of I–V relationship for total steady state currents in cardiomyocytes. Paradoxically, NH₄Cl, being added after β-NAD and having no effect on RMP, APD, and I–V curve, recovered F to the control values, indicating β-NAD/ammonia antagonism. Blocking of HCN, Kir2.x, and L-type calcium channels, Ca²⁺-activated K⁺ channels (SK, IK, and BK), or NCX exchanger reverse mode prevented this effect, indicating consistent cooperation of all currents mediated by these channels and NCX. We suggest that the activation of Kir2.x and HCN channels by extracellular K⁺, that creates positive and negative feedback, and known ammonia and K⁺ resemblance, may provide conditions required for the activation of all the chain of channels involved in the interplay. Here, we present a mechanistic model describing an interplay of channels and second messengers, which may explain discovered antagonism of β-NAD and ammonia on rat papillary muscle contractile activity. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

14 pages, 2104 KiB

Open AccessArticle

Isoliquiritigenin Protects Neuronal Cells against Glutamate Excitotoxicity

by Arina Zgodova, Svetlana Pavlova, Anastasia Nekrasova, Dmitriy Boyarkin, Vsevolod Pinelis, Alexander Surin and Zanda Bakaeva

Membranes 2022, 12(11), 1052; https://doi.org/10.3390/membranes12111052 - 27 Oct 2022

Cited by 1 | Viewed by 1465

Abstract

It is considered that glutamate excitotoxicity may be a major factor in the pathological death of neurons and mediate the development of neurodegenerative diseases in humans. Here, we show that isoliquiritigenin (ILG) at a concentration of 0.5–5 µM protects primary neuroglial cell culture [...] Read more.

It is considered that glutamate excitotoxicity may be a major factor in the pathological death of neurons and mediate the development of neurodegenerative diseases in humans. Here, we show that isoliquiritigenin (ILG) at a concentration of 0.5–5 µM protects primary neuroglial cell culture from glutamate-induced death (glutamate 100 µM). ILG (1 µM) prevented a sharp increase in [Ca²⁺]_i and a decrease in mitochondrial potential (ΔΨm). With the background action of ILG (1–5 µM), there was an increase in oxygen consumption rate (OCR) in response to glutamate, as well as in reserve respiration. The neuroprotective effect of ILG (5 µM) was accompanied by an increase in non-mitochondrial respiration. The results show that ILG can protect cortical neurons from death by preventing the development of calcium deregulation and limiting mitochondrial dysfunction caused by a high dose of glutamate. We hypothesize that ILG will be useful in drug development for the prevention or treatment of neurodegenerative diseases accompanied by glutamate excitotoxicity. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

18 pages, 6387 KiB

Open AccessArticle

Unravelling Contributions of Astrocytic Connexin 43 to the Functional Activity of Brain Neuron–Glial Networks under Hypoxic State In Vitro

by Tatiana A. Mishchenko, Roman S. Yarkov, Mariia O. Saviuk, Mikhail I. Krivonosov, Alexey D. Perenkov, Sergey V. Gudkov and Maria V. Vedunova

Membranes 2022, 12(10), 948; https://doi.org/10.3390/membranes12100948 - 28 Sep 2022

Cited by 1 | Viewed by 1570

Abstract

Brain hypoxia remains an Achilles’ heel for public health that must be urgently addressed. Hypoxic damage affects both neurons and glial cells, particularly astrocytes, which are in close dynamic bi-directional communication, and are organized in plastic and tightly regulated networks. However, astroglial networks [...] Read more.

Brain hypoxia remains an Achilles’ heel for public health that must be urgently addressed. Hypoxic damage affects both neurons and glial cells, particularly astrocytes, which are in close dynamic bi-directional communication, and are organized in plastic and tightly regulated networks. However, astroglial networks have received limited attention regarding their influence on the adaptive functional rearrangements of neural networks to oxygen deficiency. Herein, against the background of astrocytic Cx43 gap junction blockade by the selective blocker Gap19, we evaluated the features of spontaneous calcium activity and network characteristics of cells in primary cultures of the cerebral cortex, as well as the expression levels of metabotropic glutamate receptors 2 (mGluR2) and 5 (mGluR5) in the early and late periods after simulated hypoxia in vitro. We showed that, under normoxic conditions, blockade of Cx43 leads to an increase in the expression of metabotropic glutamate receptors mGluR2 and mGluR5 and long-term modulation of spontaneous calcium activity in primary cortical cultures, primarily expressed in the restructuring of the functional architectonics of neuron–glial networks through reducing the level of correlation between cells in the network and the percentage of existing correlated connections between cells. Blocking Cx43 during hypoxic injury has a pronounced neuroprotective effect. Together with the increased expression of mGluR5 receptors, a decrease in mGluR2 expression to the physiological level was found, which suggests the triggering of alternative molecular mechanisms of cell adaptation to hypoxia. Importantly, the blockade of Cx43 in hypoxic damage contributed to the maintenance of both the main parameters of the spontaneous calcium activity of primary cortical cultures and the functional architectonics of neuron–glial networks while maintaining the profile of calcium oscillations and calcium signal communications between cells at a highly correlated level. Our results demonstrate the crucial importance of astrocytic networks in functional brain adaptation to hypoxic damage and could be a promising target for the development of rational anti-hypoxic therapy. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

11 pages, 2028 KiB

Open AccessArticle

Involvement of Multidrug Resistance Modulators in the Regulation of the Mitochondrial Permeability Transition Pore

by Tatiana Fedotcheva, Nikolai Shimanovsky and Nadezhda Fedotcheva

Membranes 2022, 12(9), 890; https://doi.org/10.3390/membranes12090890 - 16 Sep 2022

Cited by 4 | Viewed by 1422

Abstract

The permeability transition pore in mitochondria (MPTP) and the ATP-binding cassette transporters (АВС transporters) in cell membranes provide the efflux of low-molecular compounds across mitochondrial and cell membranes, respectively. The inhibition of ABC transporters, especially of those related to multi drug resistance (MDR) [...] Read more.

The permeability transition pore in mitochondria (MPTP) and the ATP-binding cassette transporters (АВС transporters) in cell membranes provide the efflux of low-molecular compounds across mitochondrial and cell membranes, respectively. The inhibition of ABC transporters, especially of those related to multi drug resistance (MDR) proteins, is an actively explored approach to enhance intracellular drug accumulation and increase thereby the efficiency of anticancer therapy. Although there is evidence showing the simultaneous effect of some inhibitors on both MDR-related proteins and mitochondrial functions, their influence on MPTP has not been previously studied. We examined the participation of verapamil and quinidine, classified now as the first generation of MDR modulators, and avermectin, which has recently been actively studied as an MDR inhibitor, in the regulation of the MPTP opening. In experiments on rat liver mitochondria, we found that quinidine lowered and verapamil increased the threshold concentrations of calcium ions required for MPTP opening, and that they both decreased the rate of calcium-induced swelling of mitochondria. These effects may be associated with the positive charge of the drugs and their aliphatic properties. Avermectin not only decreased the threshold concentration of calcium ions, but also by itself induced the opening of MPTP and the mitochondrial swelling inhibited by ADP and activated by carboxyatractyloside, the substrate and inhibitor of adenine nucleotide translocase (ANT), which suggests the involvement of ANT in the process. Thus, these data indicate an additional opportunity to evaluate the effectiveness of MDR modulators in the context of their influence on the mitochondrial-dependent apoptosis. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

15 pages, 3038 KiB

Open AccessArticle

Effect of Modified Levopimaric Acid Diene Adducts on Mitochondrial and Liposome Membranes

by Mikhail V. Dubinin, Vyacheslav A. Sharapov, Alena A. Semenova, Lyudmila V. Parfenova, Anna I. Ilzorkina, Ekaterina I. Khoroshavina, Natalia V. Belosludtseva, Sergey V. Gudkov and Konstantin N. Belosludtsev

Membranes 2022, 12(9), 866; https://doi.org/10.3390/membranes12090866 - 08 Sep 2022

Cited by 2 | Viewed by 1444

Abstract

This paper demonstrates the membranotropic effect of modified levopimaric acid diene adducts on liver mitochondria and lecithin liposomes. We found that the derivatives dose-dependently reduced the efficiency of oxidative phosphorylation of mitochondria due to inhibition of the activity of complexes III and IV [...] Read more.

This paper demonstrates the membranotropic effect of modified levopimaric acid diene adducts on liver mitochondria and lecithin liposomes. We found that the derivatives dose-dependently reduced the efficiency of oxidative phosphorylation of mitochondria due to inhibition of the activity of complexes III and IV of the respiratory chain and protonophore action. This was accompanied by a decrease in the membrane potential in the case of organelle energization both by glutamate/malate (complex I substrates) and succinate (complex II substrate). Compounds 1 and 2 reduced the generation of H₂O₂ by mitochondria, while compound 3 exhibited a pronounced antioxidant effect on glutamate/malate-driven respiration and, on the other hand, caused ROS overproduction when organelles are energized with succinate. All tested compounds exhibited surface-active properties, reducing the fluidity of mitochondrial membranes and contributing to nonspecific permeabilization of the lipid bilayer of mitochondrial membranes and swelling of the organelles. Modified levopimaric acid diene adducts also induced nonspecific permeabilization of unilamellar lecithin liposomes, which confirmed their membranotropic properties. We discuss the mechanisms of action of the tested compounds on the mitochondrial OXPHOS system and the state of the lipid bilayer of membranes, as well as the prospects for the use of new modified levopimaric acid diene adducts in medicine. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Graphical abstract

18 pages, 4672 KiB

Open AccessArticle

Disulfiram Oxy-Derivatives Suppress Protein Retrotranslocation across the ER Membrane to the Cytosol and Initiate Paraptosis-like Cell Death

by Marina Solovieva, Yuri Shatalin, Irina Odinokova, Olga Krestinina, Yulia Baburina, Yana Lomovskaya, Anton Pankratov, Natalia Pankratova, Olga Buneeva, Arthur Kopylov, Alexei Medvedev and Vladimir Akatov

Membranes 2022, 12(9), 845; https://doi.org/10.3390/membranes12090845 - 29 Aug 2022

Cited by 1 | Viewed by 2077

Abstract

Disulfiram (DSF) and its derivatives were here investigated as antineoplastic agents, and their important feature is the ability to influence the UPS. We have recently shown that hydroxocobalamin catalyzes the aerobic oxidation of diethyldithiocarbamate to form disulfiram and its oxy-derivatives (DSFoxy; i.e., sulfones [...] Read more.

Disulfiram (DSF) and its derivatives were here investigated as antineoplastic agents, and their important feature is the ability to influence the UPS. We have recently shown that hydroxocobalamin catalyzes the aerobic oxidation of diethyldithiocarbamate to form disulfiram and its oxy-derivatives (DSFoxy; i.e., sulfones and sulfoxides), which induce cytoplasm vacuolization and paraptosis-like cancer cell death. We used LC-MS/MS and bioinformatics analysis to determine the key points in these processes. DSFoxy was found to induce an increase in the number of ubiquitinated proteins, including oxidized ones, and a decrease in the monomeric ubiquitin. Enhanced ubiquitination was revealed for proteins involved in the response to exogenous stress, regulation of apoptosis, autophagy, DNA damage/repair, transcription and translation, folding and ubiquitination, retrograde transport, the MAPK cascade, and some other functions. The results obtained indicate that DSF oxy-derivatives enhance the oxidation and ubiquitination of many proteins regulating proteostasis (including E3 ligases and deubiquitinases), which leads to inhibition of protein retrotranslocation across the ER membrane into the cytosol and accumulation of misfolded proteins in the ER followed by ER swelling and initiates paraptosis-like cell death. Our results provide new insight into the role of protein ubiquitination/deubiquitination in regulating protein retrotranslocation across the ER membrane into the cytosol and paraptosis-like cell death. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

16 pages, 2054 KiB

Open AccessArticle

The Short-Term Opening of Cyclosporin A-Independent Palmitate/Sr²⁺-Induced Pore Can Underlie Ion Efflux in the Oscillatory Mode of Functioning of Rat Liver Mitochondria

by Natalia V. Belosludtseva, Lyubov L. Pavlik, Konstantin N. Belosludtsev, Nils-Erik L. Saris, Maria I. Shigaeva and Galina D. Mironova

Membranes 2022, 12(7), 667; https://doi.org/10.3390/membranes12070667 - 28 Jun 2022

Cited by 1 | Viewed by 1537

Abstract

Mitochondria are capable of synchronized oscillations in many variables, but the underlying mechanisms are still unclear. In this study, we demonstrated that rat liver mitochondria, when exposed to a pulse of Sr²⁺ ions in the presence of valinomycin (a potassium ionophore) and [...] Read more.

Mitochondria are capable of synchronized oscillations in many variables, but the underlying mechanisms are still unclear. In this study, we demonstrated that rat liver mitochondria, when exposed to a pulse of Sr²⁺ ions in the presence of valinomycin (a potassium ionophore) and cyclosporin A (a specific inhibitor of the permeability transition pore complex) under hypotonia, showed prolonged oscillations in K⁺ and Sr²⁺ fluxes, membrane potential, pH, matrix volume, rates of oxygen consumption and H₂O₂ formation. The dynamic changes in the rate of H₂O₂ production were in a reciprocal relationship with the respiration rate and in a direct relationship with the mitochondrial membrane potential and other indicators studied. The pre-incubation of mitochondria with Ca²⁺(Sr²⁺)-dependent phospholipase A₂ inhibitors considerably suppressed the accumulation of free fatty acids, including palmitic and stearic acids, and all spontaneous Sr²⁺-induced cyclic changes. These data suggest that the mechanism of ion efflux from mitochondria is related to the opening of short-living pores, which can be caused by the formation of complexes between Sr²⁺(Ca²⁺) and endogenous long-chain saturated fatty acids (mainly, palmitic acid) that accumulate due to the activation of phospholipase A₂ by the ions. A possible role for transient palmitate/Ca²⁺(Sr²⁺)-induced pores in the maintenance of ion homeostasis and the prevention of calcium overload in mitochondria under pathophysiological conditions is discussed. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Graphical abstract

Review

Jump to: Research

21 pages, 2172 KiB

Open AccessReview

Potassium Ion Channels in Glioma: From Basic Knowledge into Therapeutic Applications

by Samar Younes, Nisreen Mourad, Mohamed Salla, Mohamad Rahal and Dalal Hammoudi Halat

Membranes 2023, 13(4), 434; https://doi.org/10.3390/membranes13040434 - 15 Apr 2023

Cited by 2 | Viewed by 1991

Abstract

Ion channels, specifically those controlling the flux of potassium across cell membranes, have recently been shown to exhibit an important role in the pathophysiology of glioma, the most common primary central nervous system tumor with a poor prognosis. Potassium channels are grouped into [...] Read more.

Ion channels, specifically those controlling the flux of potassium across cell membranes, have recently been shown to exhibit an important role in the pathophysiology of glioma, the most common primary central nervous system tumor with a poor prognosis. Potassium channels are grouped into four subfamilies differing by their domain structure, gating mechanisms, and functions. Pertinent literature indicates the vital functions of potassium channels in many aspects of glioma carcinogenesis, including proliferation, migration, and apoptosis. The dysfunction of potassium channels can result in pro-proliferative signals that are highly related to calcium signaling as well. Moreover, this dysfunction can feed into migration and metastasis, most likely by increasing the osmotic pressure of cells allowing the cells to initiate the “escape” and “invasion” of capillaries. Reducing the expression or channel blockage has shown efficacy in reducing the proliferation and infiltration of glioma cells as well as inducing apoptosis, priming several approaches to target potassium channels in gliomas pharmacologically. This review summarizes the current knowledge on potassium channels, their contribution to oncogenic transformations in glioma, and the existing perspectives on utilizing them as potential targets for therapy. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

22 pages, 1565 KiB

Open AccessReview

Mechanosensitive Ion Channels and Their Role in Cancer Cells

by Julia Karska, Szymon Kowalski, Jolanta Saczko, Mihaela G. Moisescu and Julita Kulbacka

Membranes 2023, 13(2), 167; https://doi.org/10.3390/membranes13020167 - 29 Jan 2023

Cited by 8 | Viewed by 4586

Abstract

Mechanical forces are an inherent element in the world around us. The effects of their action can be observed both on the macro and molecular levels. They can also play a prominent role in the tissues and cells of animals due to the [...] Read more.

Mechanical forces are an inherent element in the world around us. The effects of their action can be observed both on the macro and molecular levels. They can also play a prominent role in the tissues and cells of animals due to the presence of mechanosensitive ion channels (MIChs) such as the Piezo and TRP families. They are essential in many physiological processes in the human body. However, their role in pathology has also been observed. Recent discoveries have highlighted the relationship between these channels and the development of malignant tumors. Multiple studies have shown that MIChs mediate the proliferation, migration, and invasion of various cancer cells via various mechanisms. This could show MIChs as new potential biomarkers in cancer detection and prognosis and interesting therapeutic targets in modern oncology. Our paper is a review of the latest literature on the role of the Piezo1 and TRP families in the molecular mechanisms of carcinogenesis in different types of cancer. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

19 pages, 976 KiB

Open AccessReview

Allylamines, Benzylamines, and Fungal Cell Permeability: A Review of Mechanistic Effects and Usefulness against Fungal Pathogens

by Dalal Hammoudi Halat, Samar Younes, Nisreen Mourad and Mohamad Rahal

Membranes 2022, 12(12), 1171; https://doi.org/10.3390/membranes12121171 - 22 Nov 2022

Cited by 10 | Viewed by 3221

Abstract

Allylamines, naftifine and terbinafine, and the benzylamine, butenafine, are antifungal agents with activity on the fungal cell membrane. These synthetic compounds specifically inhibit squalene epoxidase, a key enzyme in fungal sterol biosynthesis. This results in a deficiency in ergosterol, a major fungal membrane [...] Read more.

Allylamines, naftifine and terbinafine, and the benzylamine, butenafine, are antifungal agents with activity on the fungal cell membrane. These synthetic compounds specifically inhibit squalene epoxidase, a key enzyme in fungal sterol biosynthesis. This results in a deficiency in ergosterol, a major fungal membrane sterol that regulates membrane fluidity, biogenesis, and functions, and whose damage results in increased membrane permeability and leakage of cellular components, ultimately leading to fungal cell death. With the fungal cell membrane being predominantly made up of lipids including sterols, these lipids have a vital role in the pathogenesis of fungal infections and the identification of improved therapies. This review will focus on the fungal cell membrane structure, activity of allylamines and benzylamines, and the mechanistic damage they cause to the membrane. Furthermore, pharmaceutical preparations and clinical uses of these drugs, mainly in dermatophyte infections, will be reviewed. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

13 pages, 988 KiB

Open AccessReview

The Relevance of GIRK Channels in Heart Function

by Ana Campos-Ríos, Lola Rueda-Ruzafa and José Antonio Lamas

Membranes 2022, 12(11), 1119; https://doi.org/10.3390/membranes12111119 - 09 Nov 2022

Cited by 4 | Viewed by 3305

Abstract

Among the large number of potassium-channel families implicated in the control of neuronal excitability, G-protein-gated inwardly rectifying potassium channels (GIRK/Kir3) have been found to be a main factor in heart control. These channels are activated following the modulation of G-protein-coupled receptors and, although [...] Read more.

Among the large number of potassium-channel families implicated in the control of neuronal excitability, G-protein-gated inwardly rectifying potassium channels (GIRK/Kir3) have been found to be a main factor in heart control. These channels are activated following the modulation of G-protein-coupled receptors and, although they have been implicated in different neurological diseases in both human and animal studies of the central nervous system, the therapeutic potential of different subtypes of these channel families in cardiac conditions has remained untapped. As they have emerged as a promising potential tool to treat a variety of conditions that disrupt neuronal homeostasis, many studies have started to focus on these channels as mediators of cardiac dynamics, thus leading to research into their implication in cardiovascular conditions. Our aim is to review the latest advances in GIRK modulation in the heart and their role in the cardiovascular system. Full article

(This article belongs to the Special Issue Membrane Permeability and Channels)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Membrane Permeability and Channels

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (14 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI