scholarly journals The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3131
Author(s):  
Francesco De Logu ◽  
Daniel Souza Monteiro de Araujo ◽  
Filippo Ugolini ◽  
Luigi Francesco Iannone ◽  
Margherita Vannucchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Progression ◽  
Melanoma Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Tissue Samples ◽  
Stress Signal ◽  
Transient Receptor ◽  
Melanoma Cell Lines

Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.

scholarly journals Mechanism for Regulation of Melanoma Cell Death via Activation of Thermo-TRPV4 and TRPV2

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiaojiao Zheng ◽  
Fangyuan Liu ◽  
Sha Du ◽  
Mei Li ◽  
Tian Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Melanoma Cells ◽  
Human Malignant Melanoma ◽  
Transient Receptor ◽  
A375 Cells

Background. Thermo-TRPs (temperature-sensitive transient receptor potential channels) belong to the TRP (transient receptor potential) channel superfamily. Emerging evidence implied that thermo-TRPs have been involved in regulation of cell fate in certain tumors. However, their distribution profiles and roles in melanoma remain incompletely understood. Methods. Western blot and digital PCR approaches were performed to identify the distribution profiles of six thermo-TRPs. MTT assessment was employed to detect cell viability. Flow cytometry was applied to test cell cycle and apoptosis. Calcium imaging was used to determine the function of channels. Five cell lines, including one normal human primary epidermal melanocytes and two human malignant melanoma (A375, G361) and two human metastatic melanoma (A2058, SK-MEL-3) cell lines, were chosen for this research. Results. In the present study, six thermo-TRPs including TRPV1/2/3/4, TRPA1, and TRPM8 were examined in human primary melanocytes and melanoma cells. We found that TRPV2/4, TRPA1, and TRPM8 exhibited ectopic distribution both in melanocytes and melanoma cells. Moreover, activation of TRPV2 and TRPV4 could lead to the decline of cell viability for melanoma A2058 and A375 cells. Subsequently, activation of TRPV2 by 2-APB (IC50 = 150 μM) induced cell necrosis in A2058 cells, while activation of TRPV4 by GSK1016790A (IC50 = 10 nM) enhanced apoptosis of A375 cells. Furthermore, TRPV4 mediated cell apoptosis of melanoma via phosphorylation of AKT and was involved in calcium regulation. Conclusion. Overall, our studies revealed that TRPV4 and TRPV2 mediated melanoma cell death via channel activation and characterized the mechanism of functional TRPV4 ion channel in regulating AKT pathway driven antitumor process. Thus, they may serve as potential biomarkers for the prognosis and are targeted for the therapeutic use in human melanoma.

scholarly journals Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Igor Blaha ◽  
María Elvira López-Oliva ◽  
María Pilar Martínez ◽  
Paz Recio ◽  
Ángel Agis-Torres ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Bladder Dysfunction ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Antioxidant Enzyme Activities ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Transient Receptor

Purpose. This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods. Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results. Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions. These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.

scholarly journals Transient Receptor Potential Channels as an Emerging Target for the Treatment of Parkinson’s Disease: An Insight Into Role of Pharmacological Interventions

2020 ◽  
Vol 8 ◽  
Author(s):  
Bhupesh Vaidya ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Transient Receptor

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.

scholarly journals Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors

2019 ◽  
Vol 116 (5) ◽  
pp. 1770-1775 ◽  
Author(s):  
Seung Yeon Ko ◽  
Sung Eun Wang ◽  
Han Kyu Lee ◽  
Sungsin Jo ◽  
Jinil Han ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Synaptic Function ◽  
Tissue Samples ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
The Brain ◽  
Synapsin 1

Major depressive disorder (MDD) is a devastating disease that arises in a background of environmental risk factors, such as chronic stress, that produce reactive oxygen species (ROS) in the brain. The chronic stress-induced ROS production involves Ca2+ signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+-permeable cation channel that is highly expressed in the brain. Here we show that in animal models of chronic unpredictable stress (CUS), deletion of TRPM2 (Trpm2−/−) produces antidepressant-like behaviors in mice. This phenotype correlates with reduced ROS, ROS-induced calpain activation, and enhanced phosphorylation of two Cdk5 targets including synapsin 1 and histone deacetylase 5 that are linked to synaptic function and gene expression, respectively. Moreover, TRPM2 mRNA expression is increased in hippocampal tissue samples from patients with MDD. Our findings suggest that TRPM2 is a key agent in stress-induced depression and a possible target for treating depression.

scholarly journals Glia and TRPM2 Channels in Plasticity of Central Nervous System and Alzheimer’s Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Wang ◽  
Michael F. Jackson ◽  
Yu-Feng Xie
Keyword(s):  
Oxidative Stress ◽  
Synaptic Plasticity ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Synaptic Efficacy ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channel ◽  
Trpm2 Channels ◽  
Transient Receptor

Synaptic plasticity refers to the ability of neurons to strengthen or weaken synaptic efficacy in response to activity and is the basis for learning and memory. Glial cells communicate with neurons and in this way contribute in part to plasticity in the CNS and to the pathology of Alzheimer’s disease (AD), a neurodegenerative disease in which impaired synaptic plasticity is causally implicated. The transient receptor potential melastatin member 2 (TRPM2) channel is a nonselective Ca2+-permeable channel expressed in both glial cells (microglia and astrocytes) and neurons. Recent studies indicated that TRPM2 regulates synaptic plasticity as well as the activation of glial cells. TRPM2 also modulates oxidative stress and inflammation through interaction with glial cells. As both oxidative stress and inflammation have been implicated in AD pathology, this suggests a possible contribution of TRPM2 to disease processes. Through modulating the homeostasis of glutathione, TRPM2 is involved in the process of aging which is a risk factor of AD. These results potentially point TRPM2 channel to be involved in AD through glial cells. This review summarizes recent advances in studying the contribution of TRPM2 in health and in AD pathology, with a focus on contributions via glia cells.

scholarly journals Transient Receptor Potential Melastatin 4 (TRPM4) Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury

2017 ◽  
Vol 41 (2) ◽  
pp. 835-848 ◽  
Author(s):  
Xiao-Qing Ding ◽  
Tao Ban ◽  
Zeng-Yan Liu ◽  
Jie Lou ◽  
Liang-Liang Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Salt Diet ◽  
Salt Diet ◽  
Transient Receptor Potential Melastatin ◽  
Intracellular Ros ◽  
Transient Receptor

Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli.

scholarly journals Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue

2013 ◽  
Vol 65 (3) ◽  
pp. 751-755 ◽  
Author(s):  
Mahendra Bishnoi ◽  
Kanthi Kiran Kondepudi ◽  
Aakriti Gupta ◽  
Aniket Karmase ◽  
Ravneet K. Boparai
Keyword(s):  
Adipose Tissue ◽  
Cell Lines ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Transient Receptor
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