scholarly journals Ca2+ Channel Toolkit in Neuroendocrine Tumors

2019 ◽  
Vol 110 (1-2) ◽  
pp. 147-154
Author(s):  
Alessandra Fiorio Pla ◽  
Dimitra Gkika
Keyword(s):  
Neuroendocrine Tumors ◽  
Transient Receptor Potential ◽  
Treatment Options ◽  
Unmet Need ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Neoplastic Progression ◽  
Ca2 Channels

Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies with various clinical presentations and growth rates but a common origin in neuroendocrine cells located all over the body. NET are a relatively low-frequency disease mostly represented by gastroenteropancreatic (GEP) and bronchopulmonary tumors (pNET); on the other hand, an increasing frequency and prevalence have been associated with NET. Despite great efforts in recent years, the management of NET is still a critical unmet need due to the lack of knowledge of the biology of the disease, the lack of adequate biomarkers, late presentation, the relative insensitivity of imaging modalities, and a paucity of predictably effective treatment options. In this context Ca2+ signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer, where they mediate interactions between tumor cells and the tumor microenvironment to drive different aspects of neoplastic progression (e.g., cell proliferation and survival, cell invasiveness, and proangiogenetic programs). Indeed, ion channels represent good potential pharmacological targets due to their location on the plasma membrane, where they can be easily accessed by drugs. The present review aims to provide a critical and up-to-date overview of NET development integrating Ca2+ signal involvement. In this perspective, we first give an introduction to NET and Ca2+ channels and then describe the different families of Ca2+ channels implicated in NET, i.e., ionotropic receptors, voltage-dependent Ca2+ channels, and transient receptor potential channels, as well as intracellular Ca2+ channels and their signaling molecules.

scholarly journals TRP Channels as Sensors of Aldehyde and Oxidative Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1401
Author(s):  
Katharina E. M. Hellenthal ◽  
Laura Brabenec ◽  
Eric R. Gross ◽  
Nana-Maria Wagner
Keyword(s):  
Lipid Peroxidation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Treatment Options ◽  
Receptor Potential ◽  
The Body ◽  
Trp Channel ◽  
Alcoholic Beverages ◽  
Organ Injury ◽  
Transient Receptor

The transient receptor potential (TRP) cation channel superfamily comprises more than 50 channels that play crucial roles in physiological processes. TRP channels are responsive to several exogenous and endogenous biomolecules, with aldehydes emerging as a TRP channel trigger contributing to a cellular cascade that can lead to disease pathophysiology. The body is not only exposed to exogenous aldehydes via tobacco products or alcoholic beverages, but also to endogenous aldehydes triggered by lipid peroxidation. In response to lipid peroxidation from inflammation or organ injury, polyunsaturated fatty acids undergo lipid peroxidation to aldehydes, such as 4-hydroxynonenal. Reactive aldehydes activate TRP channels via aldehyde-induced protein adducts, leading to the release of pro-inflammatory mediators driving the pathophysiology caused by cellular injury, including inflammatory pain and organ reperfusion injury. Recent studies have outlined how aldehyde dehydrogenase 2 protects against aldehyde toxicity through the clearance of toxic aldehydes, indicating that targeting the endogenous aldehyde metabolism may represent a novel treatment strategy. An addition approach can involve targeting specific TRP channel regions to limit the triggering of a cellular cascade induced by aldehydes. In this review, we provide a comprehensive summary of aldehydes, TRP channels, and their interactions, as well as their role in pathological conditions and the different therapeutical treatment options.

Concerted action of associated proteins in the regulation of TRPV5 and TRPV6

2007 ◽  
Vol 35 (1) ◽  
pp. 115-119 ◽  
Author(s):  
J.P.H. Schoeber ◽  
J.G.J. Hoenderop ◽  
R.J.M. Bindels
Keyword(s):  
Hormonal Regulation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Concerted Action ◽  
Associated Proteins ◽  
Calbindin D28k ◽  
Transient Receptor ◽  
Ca2 Channels

Ca2+ is an essential ion in all organisms and many physiological functions in the body rely on the exact maintenance of the Ca2+ balance. The epithelial Ca2+ channels TRPV5 [TRP (transient receptor potential) vanilloid 5] and TRPV6 are the most Ca2+-selective members of the TRP superfamily and are generally considered as the gatekeepers of Ca2+ entry across epithelia. TRPV5 is involved in Ca2+ reabsorption from pro-urine, while TRPV6 has an essential role in intestinal Ca2+ uptake. These channels are the prime targets of calciotropic hormonal regulation, including vitamin D and parathyroid hormone. In addition, extra- and intra-cellular signalling by associated proteins and Ca2+ itself play key roles in TRPV5 and TRPV6 regulation. In this paper, we describe the present understanding of the concerted action of calbindin-D28k, klotho and BSPRY (B-box and SPRY-domain-containing protein) at different levels throughout the epithelial cell to control Ca2+ influx at the luminal entry gate.

Abstract 164: Microdomain Specific Effects of Transient Receptor Potential Channels on Pathological Cardiac Hypertrophy and Myocyte Contractility

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Catherine A Makarewich ◽  
Hongyu Zhang ◽  
Hui Gao ◽  
Robert N Correll ◽  
Jason M Duran ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Trpc Channels ◽  
Ec Coupling ◽  
Transient Receptor ◽  
Myocyte Contractility ◽  
Signaling Domains ◽  
Ca2 Channels

Hypothesis: Ca2+ influx through transient receptor potential canonical (TRPC) channels and L-type Ca2+ channels (LTCCs) within caveolin-3 (Cav3) stabilized signaling microdomains provide a unique source of Ca2+ to activate pathologic cardiac hypertrophy through calcineurin (Cn)-mediated nuclear factor of activated T-cells (NFAT) signaling. We suggest that a distinct and separate population of TRPC channels localized in excitation-contraction (EC) coupling microdomains may have potent effects on myocyte contractility independent of Cav3 signaling domains. Methods and Results: Membrane localization studies and immunohistochemistry show that TRPC channels and LTCCs co-localize to Cav3 signaling microdomains. To explore a role for these caveolae based Ca2+ channels in the initiation of Cn-NFAT signaling we used an adenoviral NFAT-GFP reporter in cultured adult feline myocytes (AFMs). Infecting AFMs with ad-TRPC3 dramatically increased NFAT translocation, which was inhibited with dominant negative ad-dnTRPC6. Expression of a Cav3 targeted LTCC blocker (ad-Cav-Rem) reduced NFAT translocation while a targeted LTCC activator (ad-Cav-β2a) significantly increased NFAT activation. Neither LTCC modulator had significant effects on Ca2+ current or contractility in AFMs but we found that the expression of TRPC3 reduced myocyte contractility and induced spontaneous Ca2+ spark activity that was exacerbated by the DAG activator OAG. Moreover, dnTRPC6 blocked spontaneous Ca2+ sparks even in the presence of OAG. Immunohistochemistry analysis revealed the presence of TRPC channels in transverse tubules, consistent with the idea that they could have direct effects on EC coupling microdomains. Conclusions: Our data show that TRPC channels and LTCCs co-localize to Cav3 signaling domains where they generate a unique Ca2+ microenvironment that directly regulates Cn-NFAT signaling. Our findings also suggest that a separate and distinct population of TRPC channels within EC coupling microdomains cause reduced myocyte contractility by inducing SR Ca2+ leak and Ca2+ spark activity.

scholarly journals Understanding cannabinoid receptors: structure and function

2018 ◽  
Vol 14 ◽  
pp. 1-13
Author(s):  
Angelika Andrzejewska ◽  
Klaudia Staszak ◽  
Marta Kaczmarek-Ryś ◽  
Ryszard Słomski ◽  
Szymon Hryhorowicz
Keyword(s):  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Endocrine System ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Emotional States ◽  
Transient Receptor

The endocannabinoid system (ECS) consists of the endocannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade endocannabinoids. The whole EC system plays an important role in the proper functioning of the central and autonomic nervous system. ECS is involved in the regulation of the body energy and in the functioning of the endocrine system. It can affect on the regulation of emotional states, motoric movement, operations of the endocrine, immune and digestive system. Many of the effects of cannabinoids are mediated by G coupled –protein receptors: CB1, CB2 and GPR55 but also of transient receptor potential channels (TRPs) which not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In this review work we briefly summarize the role and action of cannabinoid receptors CB1 and CB2, protein-coupled receptor 55 (GPR55) and transient receptor potential vanilloid 1 (TRPV1).

scholarly journals Study on a Plasmonic Tilted Fiber Grating-Based Biosensor for Calmodulin Detection

Biosensors ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 195
Author(s):  
Xiaoyong Chen ◽  
Jie Jiang ◽  
Nan Zhang ◽  
Wenwei Lin ◽  
Pin Xu ◽  
...  
Keyword(s):  
Fiber Bragg Grating ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Nucleotide Metabolism ◽  
The Body ◽  
Bragg Grating ◽  
Fiber Grating ◽  
Potential Channels ◽  
Transient Receptor

Tilted fiber Bragg grating, which has the advantages of both fiber Bragg grating and long-period fiber grating, has been widely studied for sensing in many fields, especially in the field of biochemistry. Calmodulin, which has a wide distribution in eukaryotes, can regulate several enzymes such as adenylate cyclase and guanylate cyclase and mediates several cellular processes such as cell proliferation and cyclic nucleotide metabolism. The abnormal levels of calmodulin in the body will result in serious effects from metabolism to nerve growth and memory. Therefore, it is important to measure the calmodulin concentration in the body. In this work, we propose and experimentally demonstrate a plasmonic tilted fiber Bragg grating-based biosensor for calmodulin detection. The biosensor was made using an 18° tilted fiber Bragg grating with a 50 nm-thick gold nanofilm coating the surface of the fiber, and transient receptor potential channels were bonded onto the surface of the gold nanofilm to serve as bio-detectors for calmodulin detection. Experimental results showed that the limit of detection using our biosensor was 0.44 nM. Furthermore, we also demonstrated that the interaction between calmodulin and transient receptor potential channels was quite weak without calcium in the solution, which agrees with the biology. Our proposed biosensor has a simple structure, is easy to manufacture, and is of small size, making it a good choice for real-time, label-free, and microliter-volume biomolecule detection.

scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

scholarly journals Intractable Itch in Atopic Dermatitis: Causes and Treatments

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 229
Author(s):  
Yoshie Umehara ◽  
Chanisa Kiatsurayanon ◽  
Juan Valentin Trujillo-Paez ◽  
Panjit Chieosilapatham ◽  
Ge Peng ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Transient Receptor Potential Channels ◽  
Protease Activated Receptors ◽  
H1 Antihistamines ◽  
Potential Channels

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.

scholarly journals Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

2021 ◽  
Vol 22 (2) ◽  
pp. 778
Author(s):  
Anna Stasiłowicz ◽  
Anna Tomala ◽  
Irma Podolak ◽  
Judyta Cielecka-Piontek
Keyword(s):  
Pharmacological Activity ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Raw Material ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

scholarly journals Effects of Ginger and its Pungent Constituents on Transient Receptor Potential Channels

2017 ◽  
Vol 112 (3) ◽  
pp. 250a
Author(s):  
Young-Soo Kim ◽  
Chan Sik Hong ◽  
Sang Weon Lee ◽  
Joo Hyun Nam ◽  
Byung Joo Kim
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor
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