TRPC3-Based Protein Signaling Complex as a Therapeutic Target of Myocardial Atrophy

2020 ◽  
Vol 14 (2) ◽  
pp. 123-131
Author(s):  
Kazuhiro Nishiyama ◽  
Tomohiro Tanaka ◽  
Akiyuki Nishimura ◽  
Motohiro Nishida
Keyword(s):  
Drug Treatment ◽  
Protein Interactions ◽  
Therapeutic Target ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Interstitial Fibrosis ◽  
Receptor Potential ◽  
Cancer Drug ◽  
Myocardial Atrophy

Background: Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily members 3 (TRPC3) and 6 (TRPC6), have attracted attention as a putative therapeutic target of heart | 1 failure. Moreover, TRPC3 and TRPC6 channels are physiologically important for maintaining cellular homeostasis. How TRPC3/C6 channels alter intracellular signaling from adaptation to maladaptation has been discussed for many years. We recently showed that formation of a protein signal complex between TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional deficiency, and anticancer drug treatment) promotes Nox2-dependent reactive oxygen species production and cardiac stiffness, including myocardial atrophy and interstitial fibrosis, in rodents. In fact, pharmacological prevention of the TRPC3-Nox2 protein complex can maintain cardiac flexibility in mice after anti-cancer drug treatment. Conclusion: In this mini-review, we discuss the relationship between TRPC3/C6 channels and cardiovascular disease, and propose a new therapeutic strategy by focusing on pathology-specific protein– protein interactions.

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 TRPV4: A Physio and Pathophysiologically Significant Ion Channel

2020 ◽  
Vol 21 (11) ◽  
pp. 3837 ◽  
Author(s):  
Tamara Rosenbaum ◽  
Miguel Benítez-Angeles ◽  
Raúl Sánchez-Hernández ◽  
Sara Luz Morales-Lázaro ◽  
Marcia Hiriart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Ion Channel ◽  
Therapeutic Target ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor ◽  
Near Future ◽  
Lines Of Evidence

Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.

scholarly journals TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
María Paz Saldías ◽  
Diego Maureira ◽  
Octavio Orellana-Serradell ◽  
Ian Silva ◽  
Boris Lavanderos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ion Channels ◽  
Cancer Progression ◽  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Specific Activity ◽  
Receptor Potential ◽  
Neoplastic Disease ◽  
Transient Receptor

Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein–protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.

scholarly journals Modulation of Transient Receptor Potential (TRP) channels by tyrosine phosphorylation

2020 ◽  
Vol 3 (1) ◽  
pp. 77-87
Author(s):  
Alexandra Manolache ◽  
Teodora Stratulat ◽  
Alexandru Babeș
Keyword(s):  
Oxidative Stress ◽  
Nervous System ◽  
Tyrosine Phosphorylation ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Diverse Range ◽  
Transient Receptor ◽  
Intracellular Signaling Molecules

Transient Receptor Potential (TRP) channels are a superfamily of polymodal, non-selective receptors, expressed in the nervous system and several other tissues, where they play many physiological or pathological roles. TRP channels are sensitive to a diverse range of stimuli, such as temperature, osmolarity, oxidative stress, external compounds and intracellular signaling molecules. The activity of TRP channels can be modulated by protein phosphorylation, including tyrosine phosphorylation. In this review, we present the studies carried out so far regarding the modulation of TRP channels by tyrosine phosphorylation.

scholarly journals TRP Channels as Molecular Targets to Relieve Cancer Pain

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1
Author(s):  
Milena Duitama ◽  
Yurany Moreno ◽  
Sandra Paola Santander ◽  
Zulma Casas ◽  
Jhon Jairo Sutachan ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Peripheral Sensitization ◽  
Sensory Stimuli ◽  
Patients With Cancer ◽  
Intracellular Signaling Pathways ◽  
Transient Receptor

Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.

scholarly journals Trafficking of Stretch-Regulated TRPV2 and TRPV4 Channels Inferred Through Interactomics

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 791
Author(s):  
Pau Doñate-Macián ◽  
Jennifer Enrich-Bengoa ◽  
Irene R. Dégano ◽  
David G. Quintana ◽  
Alex Perálvarez-Marín
Keyword(s):  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Cell Structure ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Protein Interactions ◽  
Phosphoinositide Signaling ◽  
Transient Receptor ◽  
Cellular Compartments ◽  
Structure And Activity

Transient receptor potential cation channels are emerging as important physiological and therapeutic targets. Within the vanilloid subfamily, transient receptor potential vanilloid 2 (TRPV2) and 4 (TRPV4) are osmo- and mechanosensors becoming critical determinants in cell structure and activity. However, knowledge is scarce regarding how TRPV2 and TRPV4 are trafficked to the plasma membrane or specific organelles to undergo quality controls through processes such as biosynthesis, anterograde/retrograde trafficking, and recycling. This revision lists and reviews a subset of protein–protein interactions from the TRPV2 and TRPV4 interactomes, which is related to trafficking processes such as lipid metabolism, phosphoinositide signaling, vesicle-mediated transport, and synaptic-related exocytosis. Identifying the protein and lipid players involved in trafficking will improve the knowledge on how these stretch-related channels reach specific cellular compartments.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

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