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American Journal of Physiology. Cell... Jan 2019Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to... (Review)
Review
Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to induce oxidative stress and persistent inflammation. An essential feature of the clearance mechanism involves regulation of the periciliary liquid layer on the surface of the airway epithelium, which is necessary for normal ciliary beating and maintenance of mucus hydration. The underlying ion transport processes associated with airway surface hydration include epithelial Na channel-dependent Na absorption occurring in parallel with CFTR and Ca-activated Cl channel-dependent anion secretion, which are coordinately regulated to control the depth of the periciliary liquid layer. Oxidative stress is known to cause both acute and chronic effects on airway ion transport function, and an increasing number of studies in the past few years have identified an important role for autophagy as part of the physiological response to the damaging effects of oxidation. In this review, recent studies addressing the influence of oxidative stress and autophagy on airway ion transport pathways, along with results showing the potential of autophagy modulators in restoring the function of ion channels involved in transepithelial electrolyte transport necessary for effective mucociliary clearance, are presented.
Topics: Adaptor Proteins, Signal Transducing; Animals; Autophagy; Humans; Ion Transport; Mucociliary Clearance; Oxidative Stress; Respiratory Mechanics
PubMed: 30303690
DOI: 10.1152/ajpcell.00341.2018 -
Archives of Biochemistry and Biophysics Dec 2014Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in... (Review)
Review
Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis.
Topics: Animals; Calcium Signaling; Endosomes; Humans; Intracellular Membranes; Ion Channels; Ion Transport; Lysosomes; Melanins; Melanocytes; Melanosomes; Membrane Potentials; Pigmentation
PubMed: 25034214
DOI: 10.1016/j.abb.2014.06.020 -
Neuron Sep 2015Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of... (Review)
Review
Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.
Topics: Animals; Humans; Ion Channel Gating; Ion Channels; Ion Transport; Mechanotransduction, Cellular; Sensation; Touch
PubMed: 26402601
DOI: 10.1016/j.neuron.2015.08.032 -
Ion transport peptide regulates energy intake, expenditure, and metabolic homeostasis in Drosophila.Genetics Nov 2022In mammals, energy homeostasis is regulated by the antagonistic action of hormones insulin and glucagon. However, in contrast to the highly conserved insulin, glucagon...
In mammals, energy homeostasis is regulated by the antagonistic action of hormones insulin and glucagon. However, in contrast to the highly conserved insulin, glucagon is absent in most invertebrates. Although there are several endocrine regulators of energy expenditure and catabolism (such as the adipokinetic hormone), no single invertebrate hormone with all of the functions of glucagon has been described so far. Here, we used genetic gain- and loss-of-function experiments to show that the Drosophila gene Ion transport peptide (ITP) codes for a novel catabolic regulator that increases energy expenditure, lowers fat and glycogen reserves, and increases glucose and trehalose. Intriguingly, Ion transport peptide has additional functions reminiscent of glucagon, such as inhibition of feeding and transit of the meal throughout the digestive tract. Furthermore, Ion transport peptide interacts with the well-known signaling via the Adipokinetic hormone; Ion transport peptide promotes the pathway by stimulating Adipokinetic hormone secretion and transcription of the receptor AkhR. The genetic manipulations of Ion transport peptide on standard and Adipokinetic hormone-deficient backgrounds showed that the Adipokinetic hormone peptide mediates the hyperglycemic and hypertrehalosemic effects of Ion transport peptide, while the other metabolic functions of Ion transport peptide seem to be Adipokinetic hormone independent. In addition, Ion transport peptide is necessary for critical processes such as development, starvation-induced foraging, reproduction, and average lifespan. Altogether, our work describes a novel master regulator of fly physiology with functions closely resembling mammalian glucagon.
Topics: Animals; Drosophila; Glucagon; Health Expenditures; Homeostasis; Energy Intake; Ion Transport; Insulins; Mammals
PubMed: 36190340
DOI: 10.1093/genetics/iyac150 -
International Journal of Molecular... Aug 2022Na/H exchangers are essential for Na and pH homeostasis in all organisms. Human Na/H exchangers are of high medical interest, and insights into their structure and... (Review)
Review
Na/H exchangers are essential for Na and pH homeostasis in all organisms. Human Na/H exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na/H exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from has served as the prototype of Na/H exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na/H exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na/H exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na/H exchangers that explain their highly pH-regulated activity profile.
Topics: Escherichia coli; Escherichia coli Proteins; Humans; Hydrogen-Ion Concentration; Ion Transport; Sodium; Sodium-Hydrogen Exchangers
PubMed: 36012428
DOI: 10.3390/ijms23169156 -
The Chinese Journal of Dental Research 2013Primary saliva is formed by salivary epithelial endpieces through two pathways, the transcellular and the paracellular pathways. While the mechanisms of ion transport... (Review)
Review
Primary saliva is formed by salivary epithelial endpieces through two pathways, the transcellular and the paracellular pathways. While the mechanisms of ion transport through the transcellular pathway have been well studied, our understanding of fluid and electrolyte transport through the paracellular pathway remains rudimentary. Increasing evidence indicates that the tight junction (TJ) proteins form and regulate the paracellular pathway, although other intercellular junctions are probably involved. The structure of the TJ is complex and has not been well characterised. A functioning TJ is formed by multiple proteins, including membrane, cytoplasmic scaffolding, and signalling proteins. Paracellular fluid and electrolyte flow is mediated by high-capacity, charge- and size-restrictive small pores with a radius of 4 to 6 Å, whereas macromolecules pass through low-capacity, nonrestrictive large pores. Although the characteristics of these pores need to be further delineated, it is clear that they are under the regulation of the autonomic nervous system, endocrine, paracrine and autocrine systems, and various pathological factors. To date, the majority of the evidence for paracellular fluid and ion transport is accumulated from the studies using various epithelia other than salivary glands. Further investigations to explore the structure, function, and regulation of the paracellular pathway in salivary epithelia are needed to better understand the mechanism of saliva secretion.
Topics: Animals; Extracellular Fluid; Humans; Ion Transport; Saliva; Salivary Glands; Tight Junctions; Transcytosis
PubMed: 23878825
DOI: No ID Found -
Physiology (Bethesda, Md.) Sep 2017Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of... (Review)
Review
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl or non Cl anions and [Formula: see text].
Topics: Acid-Base Equilibrium; Body Fluid Compartments; Homeostasis; Humans; Hydrogen-Ion Concentration; Ion Transport; Water-Electrolyte Balance
PubMed: 28814497
DOI: 10.1152/physiol.00007.2017 -
Cells Oct 2023Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the... (Review)
Review
Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the pathophysiological mechanisms underlying epithelial transport and its significance in disease pathogenesis. Beginning with an introduction to epithelial transport, it covers various forms, including ion, water, and nutrient transfer, followed by an exploration of the processes governing ion transport and hormonal regulation. The review then addresses genetic disorders, like cystic fibrosis and Bartter syndrome, that affect epithelial transport. Furthermore, it investigates the involvement of epithelial transport in the pathophysiology of conditions such as diarrhea, hypertension, and edema. Finally, the review analyzes the impact of renal disease on epithelial transport and highlights the potential for future research to uncover novel therapeutic interventions for conditions like cystic fibrosis, hypertension, and renal failure.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Ion Transport; Hypertension
PubMed: 37887299
DOI: 10.3390/cells12202455 -
Journal of Cellular and Molecular... Sep 2020The incidence of colorectal cancer has increased annually, and the pathogenesis of this disease requires further investigation. In normal colorectal tissues, ion... (Review)
Review
The incidence of colorectal cancer has increased annually, and the pathogenesis of this disease requires further investigation. In normal colorectal tissues, ion channels and transporters maintain the water-electrolyte balance and acid/base homeostasis. However, dysfunction of these ion channels and transporters leads to the development and progression of colorectal cancer. Therefore, this review focuses on the progress in understanding the roles of ion channels and transporters in the colorectum and in colorectal cancer, including aquaporins (AQPs), Cl channels, Cl / exchangers, Na / transporters and Na /H exchangers. The goal of this review is to promote the identification of new targets for the treatment and prognosis of colorectal cancer.
Topics: Animals; Colorectal Neoplasms; Humans; Ion Channels; Ion Transport; Membrane Transport Proteins
PubMed: 32662230
DOI: 10.1111/jcmm.15600 -
Journal of the American Chemical Society Jun 2022Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a...
Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a synthetic molecular machine-like ion transport relay, in which transporters on opposite sides of a lipid bilayer membrane facilitate transport by passing ions between them. By incorporating a photo-responsive telescopic arm into the relay design, this process is reversibly controlled in response to irradiation with blue and green light. Transport occurs only in the extended state when the length of the arm is sufficient to pass the anion between transporters located on opposite sides of the membrane. In contrast, the contracted state of the telescopic arm is too short to mediate effective transport. The system acts as a stimuli-responsive ensemble of machine-like components, reminiscent of robotic arms in a factory assembly line, working cooperatively to mediate ion transport. This work points to new prospects for using lipid bilayer membranes as scaffolds for confining, orientating, and controlling the relative positions of molecular machines, thus enabling multiple components to work in concert and opening up new applications in biological contexts.
Topics: Anions; Biological Transport; Ion Channels; Ion Transport; Lipid Bilayers
PubMed: 35652660
DOI: 10.1021/jacs.2c02612