scholarly journals The Expression of Cold-Inducible RNA-Binding Protein mRNA in Sow Genital Tract Is Modulated by Natural Mating, But Not by Seminal Plasma

2020 ◽  
Vol 21 (15) ◽  
pp. 5333
Author(s):  
Jaume Gardela ◽  
Mateo Ruiz-Conca ◽  
Cristina A. Martinez ◽  
Dominic Wright ◽  
Manel López-Béjar ◽  
...  
Keyword(s):  
Ion Channels ◽  
Mrna Expression ◽  
Seminal Plasma ◽  
Genital Tract ◽  
Transient Receptor Potential ◽  
Rna Binding ◽  
Trp Channels ◽  
Rna Binding Proteins ◽  
Trp Ion Channels ◽  
Natural Mating

The RNA-binding proteins (RBPs), some of them induced by transient receptor potential (TRP) ion channels, are crucial regulators of RNA function that can contribute to reproductive pathogenesis, including inflammation and immune dysfunction. This study aimed to reveal the influence of spermatozoa, seminal plasma, or natural mating on mRNA expression of RBPs and TRP ion channels in different segments of the internal genital tract of oestrous, preovulatory sows. Particularly, we focused on mRNA expression changes of the cold-inducible proteins (CIPs) and related TRP channels. Pre-ovulatory sows were naturally mated (NM) or cervically infused with semen (Semen-AI) or sperm-free seminal plasma either from the entire ejaculate (SP-TOTAL) or the sperm-rich fraction (SP-AI). Samples (cervix to infundibulum) were collected by laparotomy under general anaesthesia for transcriptomic analysis (GeneChip® Porcine Gene 1.0 ST Array) 24 h after treatments. The NM treatment induced most of the mRNA expression changes, compared to Semen-AI, SP-AI, and SP-TOTAL treatments including unique significative changes in CIRBP, RBM11, RBM15B, RBMS1, TRPC1, TRPC4, TRPC7, and TRPM8. The findings on the differential mRNA expression on RBPs and TRP ion channels, especially to CIPs and related TRP ion channels, suggest that spermatozoa and seminal plasma differentially modulated both protein families during the preovulatory phase, probably related to a still unknown early signalling mechanism in the sow reproductive tract.

scholarly journals Dysfunction of transient receptor potential ion channels as an important pathophysiological mechanism in asthma

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Oxana Yu. Kytikova ◽  
Tatyana P. Novgorodtseva ◽  
Yulia K. Denisenko ◽  
Marina V. Antonyuk ◽  
Tatyana A. Gvozdenko
Keyword(s):  
Ion Channels ◽  
Neurogenic Inflammation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Bronchial Hyperreactivity ◽  
Pathophysiological Mechanism ◽  
Lung Pathology ◽  
Trp Ion Channels ◽  
Transient Receptor

Asthma is a chronic heterogeneous disease characterized by chronic inflammation and bronchial hyperreactivity. Neurogenic inflammation is one of the important causes of hyperreactivity. Dysfunction of transient receptor potential (TRP) ion channels underlies the development of neurogenic inflammation, bronchial hyperreactivity and respiratory symptoms of asthma such as bronchospasm and cough. TRP channels are expressed in the respiratory tract. Their activation is mediated by endogenous and exogenous factors involved in the pathogenesis of asthma. The study of functioning and regulation of TRP channels is relevant, as they could be important therapeutic targets for asthma. The aim of the review is to summarize modern ideas about the mechanisms of functioning and regulation of members of the TRP channel superfamily, the role of which in lung pathology and physiology are the best studied.

scholarly journals Functional Expression of TRP Ion Channels in Endometrial Stromal Cells of Endometriosis Patients

2018 ◽  
Vol 19 (9) ◽  
pp. 2467 ◽  
Author(s):  
Eleonora Persoons ◽  
Aurélie Hennes ◽  
Katrien De Clercq ◽  
Rita Van Bree ◽  
Goede Vriens ◽  
...  
Keyword(s):  
Ion Channels ◽  
Stromal Cells ◽  
Common Ground ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Abdominal Cavity ◽  
Functional Expression ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Trp Ion Channels

Endometriosis is a common gynecological disease that is characterized by the presence of functional endometrial-like lesions in the abdominal cavity. Aside from epithelial cells, these lesions consist of stromal cells that have the capacity to migrate, adhere, proliferate, and induce neuro- and lymphangiogenesis, which allows them to survive at ectopic locations. However, the exact underlying mechanisms that regulate these changes are yet to be elucidated. The common ground of these processes, however, is the second messenger, calcium. In this regard, members of the superfamily of transient receptor potential (TRP) ion channels, which are known to be calcium-permeable and expressed in the endometrium, have emerged as key regulators. Here, we assessed the molecular and functional expression of TRP channels in stromal cells isolated from the eutopic endometrium of endometriosis patients and controls. Using RT-qPCR, high mRNA levels of TRPV2, TRPV4, TRPM4, TRPM7, TRPC1, TRPC3, TRPC4, and TRPC6 were observed in the whole endometrium throughout the menstrual cycle. Additionally, and in line with previous reports of control patients, TRPV2, TRPV4, TRPC1/4, and TRPC6 were present in human endometrial stromal cells (hESC) from endometriosis patients both at the molecular and functional level. Moreover, proliferation and migration assays illustrated that these parameters were not affected in stromal cells from endometriosis patients. Furthermore, comparison between eutopic and ectopic endometrial samples revealed that the RNA expression pattern of TRP channels did not differ significantly. Collectively, although a functional expression of specific ion channels in hESCs was found, their expression did not correlate with endometriosis.

scholarly journals Characterization Of Selective TRPM8 Ligands And Their Structure Activity Response (S.A.R) Relationship

2010 ◽  
Vol 13 (2) ◽  
pp. 242 ◽  
Author(s):  
Muhammad Azhar Sherkheli ◽  
Angela K. Vogt-Eisele ◽  
Daniel Bura ◽  
Leopoldo R. Beltrán Márques ◽  
Günter Gisselmann ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Parent Compound ◽  
Receptor Potential ◽  
Basic Research ◽  
Fold Increase ◽  
Ring Structure ◽  
Sensory Nerves ◽  
Transient Receptor Potential Melastatin

PURPOSE: Transient receptor potential melastatin-8 (TRPM8) is an ion channel expressed extensively in sensory nerves, human prostate and overexpressed in a variety of cancers including prostate, breast, lung, colon and skin melanomas. It is activated by innoxious cooling and chemical stimuli. TRPM8 activation by cooling or chemical agonists is reported to induce profound analgesia in neuropathic pain conditions. Known TRPM8 agonists like menthol and icilin cross-activate other thermo-TRP channels like TRPV3 and TRPA1 and mutually inhibit TRPM8. This limits the usefulness of menthol and icilin as TRPM8 ligands. Consequently, the identification of selective and potent ligands for TRPM8 is of high relevance both in basic research and for therapeutic applications. In the present investigation, a group of menthol derivates was characterized. These ligands are selective and potent agonists of TRPM8. Interestingly they do not activate other thermo-TRPs like TRPA1, TRPV1, TRPV2, TRPV3 and TRPV4. These ion channels are also nociceptors and target of many inflammatory mediators. METHODS: Investigations were performed in a recombinant system: Xenopus oocytes microinjected with cRNA of gene of interest were superfused with the test substances after initial responses of known standard agonists. Evoked currents were measured by two-electrode voltage clamp technique. RESULTS: The newly characterized ligands possess an up to six-fold higher potency (EC50 in low µM) and an up to two-fold increase in efficacy compared to the parent compound menthol. In addition, it is found that chemical derivatives of menthol like CPS-368, CPS-369, CPS-125, WS-5 and WS-12 are the most selective ligands for TRPM8. The enhanced activity and selectivity seems to be conferred by hexacyclic ring structure present in all ligands as substances like WS-23 which lack this functional group activate TRPM8 with much lower potency (EC50 in mM) and those with pentacyclcic ring structure (furanone compounds) are totally inactive. CONCLUSION: The new substances activate TRPM8 with a higher potency, efficacy and specificity than menthol and will thus be of importance for the development of pharmacological agents suitable for treatment and diagnosis of certain cancers and as analgesics. STATEMENT OF NOVELTY: The new compounds have an unmatched specificity for TRPM8 ion channels with additional display of high potency and efficacy. Thus these substances are better pharmacological tools for TRPM8 characterization then known compounds and it is suggested that these menthol-derivates may serve as model substances for the development of TRPM8 ligands.

scholarly journals Deciphering the interactions of SARS-CoV-2 proteins with human ion channels using machine learning-based method

2021 ◽  
Author(s):  
Nupur S. Munjal ◽  
Dikscha Sapra ◽  
Abhishek Goyal ◽  
K.T. Shreya Parthasarathi ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ion Channels ◽  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Transmission Rate ◽  
Drug Repurposing ◽  
Receptor Potential ◽  
Ppi Networks ◽  
Approved Drugs

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the worldwide COVID-19 pandemic which began in 2019. It has a high transmission rate and pathogenicity leading to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning-based algorithms are providing higher accuracy for host-SARS-CoV-2 protein-protein interactions (PPIs). In this study, predictions of PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were performed using PPI-MetaGO algorithm. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% MCC score and 84.09% F1 score. Thereafter, PPI networks of SARS-CoV-2 proteins with HICs were generated. Furthermore, biological pathway analysis of HICs interacting with SARS-CoV-2 proteins showed the involvement of six pathways, namely inflammatory mediator regulation of TRP channels, insulin secretion, renin secretion, gap junction, taste transduction and apelin signaling pathway. The inositol 1,4,5-trisphosphate receptor 1 (ITPR1) and transient receptor potential cation channel subfamily A member 1 (TRPA1) were identified as potential target proteins. Various FDA approved drugs interacting with ITPR1 and TRPA1 are also available. It is anticipated that targeting ITPR1 and TRPA1 may provide a better therapeutic management of infection caused by SARS-CoV-2. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs.

scholarly journals Alternative Splicing Switches the Divalent Cation Selectivity of TRPM3 Channels

2005 ◽  
Vol 280 (23) ◽  
pp. 22540-22548 ◽  
Author(s):  
Johannes Oberwinkler ◽  
Annette Lis ◽  
Klaus M. Giehl ◽  
Veit Flockerzi ◽  
Stephan E. Philipp
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Splice Variants ◽  
Large Family ◽  
Ionic Selectivity ◽  
Pore Region ◽  
Cation Selectivity ◽  
Ion Conducting

TRPM3 is a poorly understood member of the large family of transient receptor potential (TRP) ion channels. Here we describe five novel splice variants of TRPM3, TRPM3α1–5. These variants are characterized by a previously unknown amino terminus of 61 residues. The differences between the five variants arise through splice events at three different sites. One of these splice sites might be located in the pore region of the channel as indicated by sequence alignment with other, better-characterized TRP channels. We selected two splice variants, TRPM3α1 and TRPM3α2, that differ only in this presumed pore region and analyzed their biophysical characteristics after heterologous expression in human embryonic kidney 293 cells. TRPM3α1 as well as TRPM3α2 induced a novel, outwardly rectifying cationic conductance that was tightly regulated by intracellular Mg2+. However, these two variants are highly different in their ionic selectivity. Whereas TRPM3α1-encoded channels are poorly permeable for divalent cations, TRPM3α2-encoded channels are well permeated by Ca2+ and Mg2+. Additionally, we found that currents through TRPM3α2 are blocked by extracellular monovalent cations, whereas currents through TRPM3α1 are not. These differences unambiguously show that TRPM3 proteins constitute a pore-forming channel subunit and localize the position of the ion-conducting pore within the TRPM3 protein. Although the ionic selectivity of ion channels has traditionally been regarded as rather constant for a given channel-encoding gene, our results show that alternative splicing can be a mechanism to produce channels with very different selectivity profiles.

Transient receptor potential ion channels as participants in thermosensation and thermoregulation

2007 ◽  
Vol 292 (1) ◽  
pp. R64-R76 ◽  
Author(s):  
Michael J. Caterina
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Core Body Temperature ◽  
Expression Patterns ◽  
Receptor Potential ◽  
Genetic Ablation ◽  
Transient Receptor ◽  
Living Organisms

Living organisms must evaluate changes in environmental and internal temperatures to mount appropriate physiological and behavioral responses conducive to survival. Classical physiology has provided a wealth of information regarding the specialization of thermosensory functions among subclasses of peripheral sensory neurons and intrinsically thermosensitive neurons within the hypothalamus. However, until recently, the molecular mechanisms by which these cells carry out thermometry have remained poorly understood. The demonstration that certain ion channels of the transient receptor potential (TRP) family can be activated by increases or decreases in ambient temperature, along with the recognition of their heterogeneous expression patterns and heterogeneous temperature sensitivities, has led investigators to evaluate these proteins as candidate endogenous thermosensors. Much of this work has involved one specific channel, TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin and related pungent vanilloid compounds and a “heat receptor,” capable of directly depolarizing neurons in response to temperatures >42°C. Evidence for a contribution of TRPV1 to peripheral thermosensation has come from pharmacological, physiological, and genetic approaches. In contrast, although capsaicin-sensitive mechanisms clearly influence core body temperature regulation, the specific contribution of TRPV1 to this process remains a matter of debate. Besides TRPV1, at least six additional thermally sensitive TRP channels have been identified in mammals, and many of these also appear to participate in thermosensation. Moreover, the identification of invertebrate TRP channels, whose genetic ablation alters thermally driven behaviors, makes it clear that thermosensation represents an evolutionarily conserved role of this ion channel family.

scholarly journals Ion channels alterations in the forebrain of high-fat diet fed rats

2021 ◽  
Vol 65 (s1) ◽  
Author(s):  
Proshanta Roy ◽  
Ilenia Martinelli ◽  
Michele Moruzzi ◽  
Federica Maggi ◽  
Consuelo Amantini ◽  
...  
Keyword(s):  
Ion Channels ◽  
Western Blot ◽  
High Fat Diet ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Acid Oxidation ◽  
Standard Diet ◽  
High Fat ◽  
Qrt Pcr

Evidence suggests that transient receptor potential (TRP) ion channels dysfunction significantly contributes to the physiopathology of metabolic and neurological disorders. Dysregulation in functions and expression in genes encoding the TRP channels cause several inherited diseases in humans (the so-called ‘TRP channelopathies’), which affect the cardiovascular, renal, skeletal, and nervous systems. This study aimed to evaluate the expression of ion channels in the forebrain of rats with diet-induced obesity (DIO). DIO rats were studied after 17 weeks under a hypercaloric diet (high-fat diet, HFD) and were compared to the control rats with a standard diet (CHOW). To determine the systemic effects of HFD exposure, we examined food intake, fat mass content, fasting glycemia, insulin levels, cholesterol, and triglycerides. qRT-PCR, Western blot, and immunochemistry analysis were performed in the frontal cortex (FC) and hippocampus (HIP). After 17 weeks of HFD, DIO rats increased their body weight significantly compared to the CHOW rats. In DIO rats, TRPC1 and TRPC6 were upregulated in the HIP, while they were downregulated in the FC. In the case of TRPM2 expression, instead was increased both in the HIP and in the FC. These could be related to the increase of proteins and nucleic acid oxidation. TRPV1 and TRPV2 gene expression showed no differences both in the FC and HIP. In general, qRT-PCR analyses were confirmed by Western blot analysis. Immunohistochemical procedures highlighted the expression of the channels in the cell body of neurons and axons, particularly for the TRPC1 and TRPC6. The alterations of TRP channel expression could be related to the activation of glial cells or the neurodegenerative process presented in the brain of the DIO rat highlighted with post synaptic protein (PSD 95) alterations. The availability of suitable animal models may be useful for studying possible pharmacological treatments to counter obesity-induced brain injury. The identified changes in DIO rats may represent the first insight to characterize the neuronal alterations occurring in obesity. Further investigations are necessary to characterize the role of TRP channels in the regulation of synaptic plasticity and obesity-related cognitive decline.

scholarly journals Deciphering the interactions of SARS-CoV-2 proteins with human ion channels using machine learning-based method

2021 ◽  
Author(s):  
Nupur S. Munjal ◽  
Dikscha Sapra ◽  
Abhishek Goyal ◽  
K.T. Shreya Parthasarathi ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ion Channels ◽  
Gap Junction ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cation Channel ◽  
Ppi Networks ◽  
Junction Protein ◽  
Transient Receptor

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the worldwide COVID-19 pandemic which began in 2019. It has a high transmission rate and pathogenicity leading to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing higher accuracy for host-SARS-CoV-2 protein-protein interactions (PPIs). In this study, predictions of PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were performed using PPI-MetaGO algorithm. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient (MCC) score and 84.09% F1 score. Thereafter, PPI networks of SARSCoV-2 proteins with HICs were generated. Furthermore, biological pathway analysis of HICs interacting with SARS-CoV-2 proteins showed the involvement of six pathways, namely inflammatory mediator regulation of transient receptor potential (TRP) channels, insulin secretion, renin secretion, gap junction, taste transduction and apelin signaling pathway. Our analysis suggests that transient receptor potential cation channel subfamily M member 4 (TRPM4), transient receptor potential cation channel subfamily A member 1 (TRPA1), gap junction protein alpha 1 (GJA1), potassium calcium-activated channel subfamily N member 4 (KCNN4), acid sensing ion channel subunit 1 (ASIC1) and inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) could serve as an initial set to the experimentalists for further validation. Additionally, various US food and drug administration (FDA) approved drugs interacting with the potential HICs were also identified. The study also reinforcesthe drug repurposing approach for the development of host directed antiviral drugs.

scholarly journals PIRT the TRP Channel Regulating Protein Binds Calmodulin and Cholesterol-Like Ligands

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 478 ◽  
Author(s):  
Nicholas J. Sisco ◽  
Dustin D. Luu ◽  
Minjoo Kim ◽  
Wade D. Van Horn
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Transmembrane Helix ◽  
Receptor Potential ◽  
Outer Leaflet ◽  
Heat Sensor ◽  
Transient Receptor ◽  
Α Helix ◽  
Obesity And Cancer

Transient receptor potential (TRP) ion channels are polymodal receptors that have been implicated in a variety of pathophysiologies, including pain, obesity, and cancer. The capsaicin and heat sensor TRPV1, and the menthol and cold sensor TRPM8, have been shown to be modulated by the membrane protein PIRT (Phosphoinositide-interacting regulator of TRP). The emerging mechanism of PIRT-dependent TRPM8 regulation involves a competitive interaction between PIRT and TRPM8 for the activating phosphatidylinositol 4,5-bisphosphate (PIP2) lipid. As many PIP2 modulated ion channels also interact with calmodulin, we investigated the possible interaction between PIRT and calmodulin. Using microscale thermophoresis (MST), we show that calmodulin binds to the PIRT C-terminal α-helix, which we corroborate with a pull-down experiment, nuclear magnetic resonance-detected binding study, and Rosetta-based computational studies. Furthermore, we identify a cholesterol-recognition amino acid consensus (CRAC) domain in the outer leaflet of the first transmembrane helix of PIRT, and with MST, show that PIRT specifically binds to a number of cholesterol-derivatives. Additional studies identified that PIRT binds to cholecalciferol and oxytocin, which has mechanistic implications for the role of PIRT regulation of additional ion channels. This is the first study to show that PIRT specifically binds to a variety of ligands beyond TRP channels and PIP2.

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