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Cell Biochemistry and Function Jun 2024Potassium bromate (KBrO) is a common dietary additive, pharmaceutical ingredient, and significant by-product of water disinfection. p-coumaric acid (PCA) is a naturally...
Potassium bromate (KBrO) is a common dietary additive, pharmaceutical ingredient, and significant by-product of water disinfection. p-coumaric acid (PCA) is a naturally occurring nutritional polyphenolic molecule with anti-inflammatory and antioxidant activities. The goal of the current investigation was to examine the protective effects of p-coumaric acid against the liver damage caused by KBrO. The five groups of animals-control, KBrO (100 mg/kg bw), treatment with KBrO along with Silymarin (100 mg/kg bw), KBrO followed by PCA (100 mg/bw, and 200 mg/kg bw) were randomly assigned to the animals. Mice were slaughtered, and blood and liver tissues were taken for assessment of the serum biochemical analysis for markers of liver function (alanine transaminase, aspartate transaminase, alkaline phosphatase, albumin, and protein), lipid markers and antioxidant markers (TBARS), glutathione peroxidase [GSH-Px], glutathione (GSH), and markers of hepatic oxidative stress (CAT), (SOD), as well as histological H&E stain, immunohistochemical stain iNOS, and COX-2 as markers of inflammatory cytokines. PCA protects against acute liver failure by preventing the augmentation of blood biochemical markers and lipid profiles. In mice liver tissues, KBrO increases lipid indicators and depletes antioxidants, leading to an increase in JNK, ERK, and p38 phosphorylation. Additionally, PCA inhibited the production of pro-inflammatory cytokines and reduced the histological alterations in KBrO-induced hepatotoxicity. Notably, PCA effectively mitigated KBrO-induced hepatic damage by obstructing the TNF-α/NF-kB-mediated inflammatory process signaling system. Additionally, in KBrO-induced mice, PCA increased the intensities of hepatic glutathione (GSH), SOD, GSH-Px, catalase, and GSH activities. Collectively, we demonstrate the molecular evidence that PCA eliminated cellular inflammatory conditions, mitochondrial oxidative stress, and the TNF-α/NF-κB signaling process, thereby preventing KBrO-induced hepatocyte damage.
Topics: Animals; Mice; Coumaric Acids; Bromates; Liver; Propionates; Male; Oxidative Stress; Chemical and Drug Induced Liver Injury; Antioxidants; Protective Agents
PubMed: 38895919
DOI: 10.1002/cbf.4076 -
Materials Horizons Jun 2024Porous crystalline conjugated macrocyclic materials (CMMs) possess high porosity, tunable structure/function and efficient charge transport ability owing to their planar... (Review)
Review
Porous crystalline conjugated macrocyclic materials (CMMs) possess high porosity, tunable structure/function and efficient charge transport ability owing to their planar macrocyclic conjugated π-electron system, which make them promising candidates for applications in energy storage. In this review, we thoroughly summarize the timely development of porous crystalline CMMs in energy storage related fields. Specifically, we summarize and discuss their structures and properties. In addition, their energy storage applications, such as lithium ion batteries, lithium sulfur batteries, sodium ion batteries, potassium ion batteries, Li-CO batteries, Li-O batteries, Zn-air batteries, supercapacitors and triboelectric nanogenerators, are also discussed. Finally, we present the existing challenges and future prospects. We hope this review will inspire the development of advanced energy storage materials based on porous crystalline CMMs.
PubMed: 38895771
DOI: 10.1039/d4mh00313f -
The Journal of Physical Chemistry. C,... Jun 2024Zeolites contain extraframework cations that are exchangeable under favorable aqueous conditions; this is the fundamental feature for their application in water...
Zeolites contain extraframework cations that are exchangeable under favorable aqueous conditions; this is the fundamental feature for their application in water purification and necessary to produce cation forms for other applications such as catalysis. Optimization of the process is common, but there is little fundamental understanding based on real-time experiments of the mechanism of exchange for most zeolites. The sodium and potassium forms of zeolite chabazite selectively uptake Cs by ion exchange, leading to its application in removing radioactive Cs from industrial nuclear waste streams, as well as from contaminated environments in the aftermath of the Fukushima and Three Mile Island accidents. In this study, synchrotron powder X-ray diffraction patterns have been collected on chabazite as it undergoes Cs-ion exchange. Applying Rietveld refinement to these patterns has revealed the time-resolved structural changes that occur in the zeolite as exchange progresses, charting the changes in the spatial distribution of the extraframework cations and water molecules in the structure during the reaction. Ultimately, a detailed mechanistic understanding of how this dynamic ion-exchange reaction occurs has been obtained.
PubMed: 38894753
DOI: 10.1021/acs.jpcc.4c02145 -
Molecules (Basel, Switzerland) May 2024Gain-of-function mutations in the gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental...
Gain-of-function mutations in the gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor () discovered via a high-throughput screen. Across three distinct regions of the chemotype, we synthesized 58 new analogs and tested each one in a whole-cell automated patch-clamp assay to develop structure-activity relationships for inhibition of SLACK channels. We further evaluated selected analogs for their selectivity versus a variety of other ion channels and for their activity versus clinically relevant SLACK mutants. Selectivity within the series was quite good, including versus hERG. Analog (VU0948578) was a potent inhibitor of WT, A934T, and G288S SLACK, with IC values between 0.59 and 0.71 µM across these variants. VU0948578 represents a useful in vitro tool compound from a chemotype that is distinct from previously reported small molecule inhibitors of SLACK channels.
Topics: Structure-Activity Relationship; Humans; Potassium Channel Blockers; Potassium Channels, Sodium-Activated; Nerve Tissue Proteins; Xanthine; Patch-Clamp Techniques; HEK293 Cells; Molecular Structure; Xanthines
PubMed: 38893312
DOI: 10.3390/molecules29112437 -
International Journal of Molecular... Jun 2024The strength of inhibitory neurotransmission depends on intracellular neuronal chloride concentration, primarily regulated by the activity of cation-chloride...
The strength of inhibitory neurotransmission depends on intracellular neuronal chloride concentration, primarily regulated by the activity of cation-chloride cotransporters NKCC1 (Sodium-Potassium-Chloride Cotransporter 1) and KCC2 (Potassium-Chloride Cotransporter 2). Brain-derived neurotrophic factor (BDNF) influences the functioning of these co-transporters. BDNF is synthesized from precursor proteins (proBDNF), which undergo proteolytic cleavage to yield mature BDNF (mBDNF). While previous studies have indicated the involvement of BDNF signaling in the activity of KCC2, its specific mechanisms are unclear. We investigated the interplay between both forms of BDNF and chloride homeostasis in rat hippocampal neurons and in utero electroporated cortices of rat pups, spanning the behavioral, cellular, and molecular levels. We found that both pro- and mBDNF play a comparable role in immature neurons by inhibiting the capacity of neurons to extrude chloride. Additionally, proBDNF increases the endocytosis of KCC2 while maintaining a depolarizing shift of E in maturing neurons. Behaviorally, proBDNF-electroporated rat pups in the somatosensory cortex exhibit sensory deficits, delayed huddling, and cliff avoidance. These findings emphasize the role of BDNF signaling in regulating chloride transport through the modulation of KCC2. In summary, this study provides valuable insights into the intricate interplay between BDNF, chloride homeostasis, and inhibitory synaptic transmission, shedding light on the underlying cellular mechanisms involved.
Topics: Animals; Brain-Derived Neurotrophic Factor; Symporters; K Cl- Cotransporters; Neurons; Rats; Homeostasis; Chlorides; Hippocampus; Female; Protein Precursors; Cells, Cultured; Solute Carrier Family 12, Member 2
PubMed: 38892438
DOI: 10.3390/ijms25116253 -
International Journal of Molecular... Jun 2024The sodium pump, or Na/K-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na) and... (Review)
Review
The sodium pump, or Na/K-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na) and potassium (K) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA's role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell-cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells.
Topics: Sodium-Potassium-Exchanging ATPase; Animals; Humans; Cell Membrane; Signal Transduction; Ouabain; Cardiac Glycosides; Sodium
PubMed: 38892309
DOI: 10.3390/ijms25116122 -
International Journal of Molecular... May 2024The sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin is increasingly used in the treatment of diabetes and heart failure. Dapagliflozin has been...
The sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin is increasingly used in the treatment of diabetes and heart failure. Dapagliflozin has been associated with reduced incidence of atrial fibrillation (AF) in clinical trials. We hypothesized that the favorable antiarrhythmic outcome of dapagliflozin use may be caused in part by previously unrecognized effects on atrial repolarizing potassium (K) channels. This study was designed to assess direct pharmacological effects of dapagliflozin on cloned ion channels K11.1, K1.5, K4.3, K2.1, K2.1, K3.1, and K17.1, contributing to , , , , and K currents. Human channels coded by , , , , , , and were heterologously expressed in oocytes, and currents were recorded using the voltage clamp technique. Dapagliflozin (100 µM) reduced K11.1 and K1.5 currents, whereas K2.1, K2.1, and K17.1 currents were enhanced. The drug did not significantly affect peak current amplitudes of K4.3 or K3.1 K channels. Biophysical characterization did not reveal significant effects of dapagliflozin on current-voltage relationships of study channels. In conclusion, dapagliflozin exhibits direct functional interactions with human atrial K channels underlying , , , and currents. Substantial activation of K2.1 and K17.1 currents could contribute to the beneficial antiarrhythmic outcome associated with the drug. Indirect or chronic effects remain to be investigated in vivo.
Topics: Humans; Glucosides; Sodium-Glucose Transporter 2 Inhibitors; Benzhydryl Compounds; Animals; Xenopus laevis; Potassium Channels; Oocytes; Sodium-Glucose Transporter 2
PubMed: 38891889
DOI: 10.3390/ijms25115701 -
International Journal of Molecular... May 2024Two genes of nitrate transporters and , putative orthologs of high-affinity nitrate transporter genes and from , were cloned from the euhalophyte . Phylogenetic...
Two genes of nitrate transporters and , putative orthologs of high-affinity nitrate transporter genes and from , were cloned from the euhalophyte . Phylogenetic bioinformatic analysis demonstrated that the proteins SaNRT2.1 and SaNRT2.5 exhibited higher levels of homology to the corresponding proteins from the plants of family Amaranthaceae; the similarity of amino acid sequences between proteins SaNRT2.1 and SaNRT2.5 was lower (54%). Both SaNRT2.1 and SaNRT2.5 are integral membrane proteins forming 12 transmembrane helices as predicted by topological modeling. An attempt to demonstrate nitrate transporting activity of or by heterologous expression of the genes in the yeast () mutant strain Δ lacking the only yeast nitrate transporter was not successful. The expression patterns of and were studied in plants that were grown in hydroponics under either low (0.5 mM) or high (15 mM) nitrate and salinity from 0 to 750 mM NaCl. The growth of the plants was strongly inhibited by low nitrogen supply while stimulated by NaCl; it peaked at 250 mM NaCl for high nitrate and at 500 mM NaCl for low nitrate. Under low nitrate supply, nitrate contents in roots, leaves and stems were reduced but increased in leaves and stems as salinity in the medium increased. Potassium contents remained stable under salinity treatment from 250 to 750 mM NaCl. Quantitative real-time PCR demonstrated that without salinity, was expressed in all organs, its expression was not influenced by nitrate supply, while was expressed exclusively in roots-its expression rose about 10-fold under low nitrate. Salinity increased expression of both and under low nitrate. peaked in roots at 500 mM NaCl with 15-fold increase; peaked in roots at 500 mM NaCl with 150-fold increase. It is suggested that SaNRT2.5 ensures effective nitrate uptake by roots and functions as an essential high-affinity nitrate transporter to support growth of adult plants under nitrogen deficiency.
Topics: Nitrate Transporters; Cloning, Molecular; Plant Proteins; Anion Transport Proteins; Phylogeny; Nitrates; Gene Expression Regulation, Plant; Chenopodiaceae; Amino Acid Sequence; Plant Roots
PubMed: 38891835
DOI: 10.3390/ijms25115648 -
Polymers May 2024This paper reports the successful development and application of an efficient method for quantifying Pb in aqueous samples using a smartphone-based colorimetric device...
This paper reports the successful development and application of an efficient method for quantifying Pb in aqueous samples using a smartphone-based colorimetric device with an imprinted polymer (IIP). The IIP was synthesized by modifying the previous study; using rhodizonate, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), ,'-methylenebisacrylamide (MBA), and potassium persulfate (KPS). The polymers were then characterized. An absorption study was performed to determine the optimal conditions for the smartphone-based colorimetric device processing. The device consists of a black box (10 × 10 × 10 cm), which was designed to ensure repeatability of the image acquisition. The methodology involved the use of a smartphone camera to capture images of IIP previously exposed at Pb solutions with various concentrations, and color channel values were calculated (RGB, YMK HSVI). PLS multivariate regression was performed, and the optimum working range (0-10 mg L) was determined using seven principal components with a detection limit (LOD) of 0.215 mg L and R = 0.998. The applicability of a colorimetric sensor in real samples showed a coefficient of variation (% RSD) of less than 9%, and inductively coupled plasma mass spectrometry (ICP-MS) was applied as the reference method. These results confirmed that the quantitation smartphone-based colorimetric sensor is a suitable analytical tool for reliable on-site Pb monitoring.
PubMed: 38891469
DOI: 10.3390/polym16111523 -
Cells May 2024Pacemaking activity in substantia nigra dopaminergic neurons is generated by the coordinated activity of a variety of distinct somatodendritic voltage- and calcium-gated...
High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons.
Pacemaking activity in substantia nigra dopaminergic neurons is generated by the coordinated activity of a variety of distinct somatodendritic voltage- and calcium-gated ion channels. We investigated whether these functional interactions could arise from a common localization in macromolecular complexes where physical proximity would allow for efficient interaction and co-regulations. For that purpose, we immunopurified six ion channel proteins involved in substantia nigra neuron autonomous firing to identify their molecular interactions. The ion channels chosen as bait were Cav1.2, Cav1.3, HCN2, HCN4, Kv4.3, and SK3 channel proteins, and the methods chosen to determine interactions were co-immunoprecipitation analyzed through immunoblot and mass spectrometry as well as proximity ligation assay. A macromolecular complex composed of Cav1.3, HCN, and SK3 channels was unraveled. In addition, novel potential interactions between SK3 channels and sclerosis tuberous complex (Tsc) proteins, inhibitors of mTOR, and between HCN4 channels and the pro-degenerative protein Sarm1 were uncovered. In order to demonstrate the presence of these molecular interactions in situ, we used proximity ligation assay (PLA) imaging on midbrain slices containing the substantia nigra, and we could ascertain the presence of these protein complexes specifically in substantia nigra dopaminergic neurons. Based on the complementary functional role of the ion channels in the macromolecular complex identified, these results suggest that such tight interactions could partly underly the robustness of pacemaking in dopaminergic neurons.
Topics: Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Proteomics; Dopaminergic Neurons; Animals; Small-Conductance Calcium-Activated Potassium Channels; Mesencephalon; Humans; Calcium Channels, L-Type; Mice; Substantia Nigra
PubMed: 38891076
DOI: 10.3390/cells13110944