scholarly journals Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions

2019 ◽  
Author(s):  
Subhransu Sekhar Sahoo ◽  
Rakesh Kumar Majhi ◽  
Ankit Tiwari ◽  
Tusar Acharya ◽  
P Sanjai Kumar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Transient Receptor Potential ◽  
Specific Inhibitor ◽  
Receptor Potential ◽  
Endogenous Expression ◽  
Intracellular Ca ◽  
Transient Receptor

AbstractTransient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface. TRPA1-specific activator namely AITC increases intracellular Ca2+-levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+-levels in T cells. Such Ca2+-influx can also be influenced by chelation of intracellular Ca2+ as well as extracellular Ca2+. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN-γ and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.

scholarly journals Transient receptor potential ankyrin1 channel is endogenously expressed in T cells and is involved in immune functions

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Subhransu Sekhar Sahoo ◽  
Rakesh Kumar Majhi ◽  
Ankit Tiwari ◽  
Tusar Acharya ◽  
P. Sanjai Kumar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Endogenous Expression ◽  
Transient Receptor ◽  
Cluster Of Differentiation

Abstract Transient receptor potential channel subfamily A member 1 (TRPA1) is a non-selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the information on the role of TRPA1 toward T-cell responses remains scanty. In silico data suggest that TRPA1 can play an important role in the T-cell activation process. In this work, we explored the endogenous expression of TRPA1 and its function in T cells. By reverse transcription polymerase chain reaction (RT-PCR), confocal microscopy and flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. TRPA1 is primarily located at the cell surface. TRPA1-specific activator namely allyl isothiocyanate (AITC) increases intracellular calcium ion (Ca2+) levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+ levels in T cells; TRPA1 inhibition also reduces TCR-mediated calcium influx. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or Concanavalin A (ConA)-driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of cluster of differentiation 25 (CD25), cluster of differentiation 69 (CD69) in ConA/TCR stimulated T cells and secretion of cytokines like tumor necrosis factor (TNF), interferon γ (IFN-γ), and interleukin 2 (IL-2) suggesting that endogenous activity of TRPA1 may be involved in T-cell activation. Collectively these results may have implication in T cell-mediated responses and indicate possible role of TRPA1 in immunological disorders.

Role of capacitative Ca2+ entry in bronchial contraction and remodeling

2002 ◽  
Vol 92 (4) ◽  
pp. 1594-1602 ◽  
Author(s):  
Michele Sweeney ◽  
Sharon S. McDaniel ◽  
Oleksandr Platoshyn ◽  
Shen Zhang ◽  
Ying Yu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Bronchial Hyperresponsiveness ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Wall Thickening ◽  
Bronchial Wall ◽  
Intracellular Ca ◽  
Transient Receptor

Asthma is characterized by airway inflammation, bronchial hyperresponsiveness, and airway obstruction by bronchospasm and bronchial wall thickening due to smooth muscle hypertrophy. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) may serve as a shared signal transduction element that causes bronchial constriction and bronchial wall thickening in asthma. In this study, we examined whether capacitative Ca2+ entry (CCE) induced by depletion of intracellular Ca2+ stores was involved in agonist-mediated bronchial constriction and bronchial smooth muscle cell (BSMC) proliferation. In isolated bronchial rings, acetylcholine (ACh) induced a transient contraction in the absence of extracellular Ca2+ because of Ca2+ release from intracellular Ca2+ stores. Restoration of extracellular Ca2+in the presence of atropine, an M-receptor blocker, induced a further contraction that was apparently caused by a rise in [Ca2+]cyt due to CCE. In single BSMC, amplitudes of the store depletion-activated currents ( I SOC) and CCE were both enhanced when the cells proliferate, whereas chelation of extracellular Ca2+ with EGTA significantly inhibited the cell growth in the presence of serum. Furthermore, the mRNA expression of TRPC1, a transient receptor potential channel gene, was much greater in proliferating BSMC than in growth-arrested cells. Blockade of the store-operated Ca2+channels by Ni2+ decreased I SOC and CCE and markedly attenuated BSMC proliferation. These results suggest that upregulated TRPC1 expression, increased I SOC, enhanced CCE, and elevated [Ca2+]cyt may play important roles in mediating bronchial constriction and BSMC proliferation.

TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells

2004 ◽  
Vol 287 (2) ◽  
pp. C357-C364 ◽  
Author(s):  
Xiaoxia Wang ◽  
Jennifer L. Pluznick ◽  
Peilin Wei ◽  
Babu J. Padanilam ◽  
Steven C. Sansom
Keyword(s):  
Transient Receptor Potential ◽  
Mesangial Cells ◽  
Receptor Potential ◽  
Immunocytochemical Staining ◽  
Rt Pcr ◽  
Fura 2 ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Ca2 Channels

Studies were performed to identify the molecular component responsible for store-operated Ca2+ entry in murine mesangial cells (MMC). Because the canonical transient receptor potential (TRPC) family of proteins was previously shown to comprise Ca2+-selective and -nonselective cation channels in a variety of cells, we screened TRPC1–TRPC7 with the use of molecular methods and the fura 2 method to determine their participation as components of the mesangial store-operated Ca2+ (SOC) channel. Using TRPC-specific primers and RT-PCR, we found that cultured MMC contained mRNA for TRPC1 and TRPC4 but not for TRPC2, TRPC3, TRPC5, TRPC6, and TRPC7. Immunocytochemical staining of MMC revealed predominantly cytoplasmic expression of TRPC1 and plasmalemmal expression of TRPC4. The role of TRPC4 in SOC was determined with TRPC4 antisense and fura 2 ratiometric measurements of intracellular Ca2+ concentration ([Ca2+]i). SOC was measured as the increase in [Ca2+]i after extracellular Ca2+ was increased from <10 nM to 1 mM in the continued presence of thapsigargin. We found that TRPC4 antisense, which reduced plasmalemmal expression of TRPC4, inhibited SOC by 83%. Incubation with scrambled TRPC4 oligonucleotides did not affect SOC. Immunohistochemical staining identified expressed TRPC4 in the glomeruli of mouse renal sections. The results of RT-PCR performed to distinguish between TRPC4-α and TRPC4-β were consistent with expression of both isoforms in brain but with only TRPC4-α expression in MMC. These studies show that TRPC4-α may form the homotetrameric SOC in mouse mesangial cells.

RPC6 Up-Regulation in Ang II-Induced Podocyte Apoptosis Might Result from ERK Activation and NF-κB Translocation

2009 ◽  
Vol 234 (9) ◽  
pp. 1029-1036 ◽  
Author(s):  
Han Zhang ◽  
Jie Ding ◽  
Qingfeng Fan ◽  
Shufang Liu
Keyword(s):  
Transient Receptor Potential ◽  
Specific Inhibitor ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Erk Pathway ◽  
Ang Ii ◽  
Extracellular Signal ◽  
Intracellular Ca ◽  
Apoptosis Inducer ◽  
Transient Receptor

Angiotensin II (Ang II) has been recognized as an apoptosis inducer in podocytes, but the mechanism of apoptosis induced by Ang II is unclear. Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane. The present study evaluated the alteration of TRPC6 expression and the Ca2+ influx involved in Ang II-induced podocyte apoptosis. The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated. The apoptosis of mouse podocytes (MPC5) was induced by Ang II. The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca2+ concentration was elevated. By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca2+ influx were inhibited. Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-κB (NF-κB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased. Moreover, the translocation of NF-κB in nucleus resulted from Ang II was reduced by treatment with U0126. In conclusion, the enhancement expression of TRPC6 as well as the increased Ca2+ influx mediated by TRPC6 channels contributed to the podocyte apoptosis. The activation of ERK pathway and subsequent translocation of NF-κB was possibly necessary for the up-regulation TRPC6 induced by Ang II.

scholarly journals Plasma membrane localization and function of TRPC1 is dependent on its interaction with β-tubulin in retinal epithelium cells

2005 ◽  
Vol 22 (2) ◽  
pp. 163-170 ◽  
Author(s):  
SUNITHA BOLLIMUNTHA ◽  
ERIC CORNATZER ◽  
BRIJ B SINGH
Keyword(s):  
Plasma Membrane ◽  
Transient Receptor Potential ◽  
Retinal Pigment ◽  
Receptor Potential ◽  
Retinal Cells ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
And Function ◽  
Β Tubulin

Mammalian homologues of the Drosophila canonical Transient Receptor Potential (TRPC) protein have been proposed to encode the store-operated Ca2+ influx (SOC) channel(s). This study examines the role of TRPC1 in the SOC mechanism of retinal cells. htrpc1 transcript was detected in bovine retinal and in human adult retinal pigment epithelial (ARPE) cells. Western blot analysis also confirmed the expression of TRPC1 protein in neuronal cells including retina and ARPE cells. To determine the role of TRPC1 protein in retinal cells, TRPC1 was recombinantly expressed in ARPE cells and changes in intracellular Ca2+ were analyzed. ARPE cells stably transfected with htrp1 cDNA displayed 2-fold higher Ca2+ influx with no significant increase in the basal influx. Consistent with this the overexpressed TRPC1 protein was localized in the plasma membrane region of ARPE cells. Interestingly, both bovine retinal tissues and ARPE cells showed that TRPC1 protein co-localizes and could be co-immunoprecipitated with β-tubulin. Disruption of tubulin by colchicine significantly decreased both plasma membrane staining of the TRPC1 protein and Ca2+ influx in ARPE cells. These results suggest that TRPC1 channel protein is expressed in retinal cells, further, targeting/retention of the TRPC1 protein to the plasma membrane in retinal cells is mediated via its interaction with β-tubulin.

scholarly journals Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light

2009 ◽  
Vol 297 (3) ◽  
pp. C679-C687 ◽  
Author(s):  
Sulochana Devi ◽  
Rajendra Kedlaya ◽  
Nityanand Maddodi ◽  
Kumar M. R. Bhat ◽  
Craig S. Weber ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ultraviolet B ◽  
Pigment Cells ◽  
Metastasis Suppressor ◽  
Melanoma Metastasis ◽  
Transient Receptor Potential Melastatin ◽  
Intracellular Ca ◽  
Transient Receptor

Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca2+ levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role for TRPM1 in Ca2+ homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca2+ and uptake of extracellular Ca2+. These data suggest a role for TRPM1-mediated Ca2+ homeostasis, which is also regulated by ultraviolet B, in melanogenesis.

scholarly journals PRMT5 promotes symmetric dimethylation of RNA processing proteins and modulates activated T cell alternative splicing and Ca2+/NFAT signaling

2021 ◽  
Author(s):  
Shouvonik Sengupta ◽  
Kelsi O. West ◽  
Shridhar Sanghvi ◽  
Georgios Laliotis ◽  
Laura M. Agosto ◽  
...  
Keyword(s):  
T Cells ◽  
Alternative Splicing ◽  
T Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Major Type ◽  
Activated T Cells ◽  
Th Cell ◽  
Activated T Cell ◽  
Transient Receptor

AbstractProtein Arginine Methyltransferase (PRMT) 5 is the major type 2 methyltransferase catalyzing symmetric dimethylation (SDM) of arginine. PRMT5 inhibition or deletion in CD4 Th cells reduces TcR engagement-induced IL-2 production and Th cell expansion and confers protection against experimental autoimmune encephalomyelitis (EAE), the animal model of Multiple Sclerosis. However, the mechanisms by which PRMT5 modulates T helper (Th) cell proliferation are still not completely understood and neither are the methylation targets in T cells. In this manuscript, we uncover the role of PRMT5 on alternative splicing (AS) in activated T cells and identify several targets of PRMT5 SDM involved in splicing. In addition, we find a possible link between PRMT5 mediated AS of Trpm4 (Transient Receptor Potential Cation Channel Subfamily M Member 4) and TcR/NFAT signaling/IL-2 production. This understanding may guide development of drugs targeting these processes to benefit patients with T cell-mediated diseases.

scholarly journals Store-operated Ca2+ entry: a key component of the insulin secretion machinery

2016 ◽  
Vol 57 (3) ◽  
pp. F35-F39 ◽  
Author(s):  
Jessica Sabourin ◽  
Florent Allagnat
Keyword(s):  
Insulin Secretion ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Leading Role ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Insulin Exocytosis

Normal plasma glucose level is ensured by the action of insulin, the major hypoglycemic hormone. Therefore, it is not surprising that insulin release from pancreatic β-cells of the islets of Langerhans is controlled by an array of balanced mechanisms in which glucose plays the leading role. Glucose triggers insulin secretion through the well-described pathway of ATP-driven closure of ATP-sensitive potassium channels (KATP), depolarization of the plasma membrane, and opening of the voltage-dependent Ca2+ channels (VDCC). The subsequent rapid rise in cytoplasmic free Ca2+ concentration triggers insulin exocytosis. However, despite more than 40 years of investigation, certain aspects of the intracellular Ca2+ responses to glucose and secretagogues remain unexplained, suggesting the involvement of additional Ca2+ channels. Here, we discuss the emerging role of store-operated Ca2+ channels carried by Orai1 and transient receptor potential canonical 1 (TRPC1) proteins and regulated by the stromal interaction molecule 1 (STIM1) in the control of glucose-induced insulin secretion. The role of other voltage-independent cation channels formed by other members of the TRP channels family is also addressed.

scholarly journals Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall
Keyword(s):  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

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