scholarly journals Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2

2018 ◽  
Vol 19 (9) ◽  
pp. 2829 ◽  
Author(s):  
Katja Eubler ◽  
Carola Herrmann ◽  
Astrid Tiefenbacher ◽  
Frank-Michael Köhn ◽  
J. Schwarzer ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Angiogenic Factor ◽  
Human Testis ◽  
Seminiferous Tubules ◽  
Protein Levels ◽  
Peritubular Cells

Peritubular cells are part of the wall of seminiferous tubules in the human testis and their contractile abilities are important for sperm transport. In addition, they have immunological roles. A proteomic analysis of isolated human testicular peritubular cells (HTPCs) revealed expression of the transient receptor potential channel subfamily V member 2 (TRPV2). This cation channel is linked to mechano-sensation and to immunological processes and inflammation in other organs. We verified expression of TRPV2 in peritubular cells in human sections by immunohistochemistry. It was also found in other testicular cells, including Sertoli cells and interstitial cells. In cultured HTPCs, application of cannabidiol (CBD), a known TRPV2 agonist, acutely induced a transient increase in intracellular Ca2+ levels. These Ca2+ transients could be blocked both by ruthenium red, an unspecific Ca2+ channel blocker, and tranilast (TRA), an antagonist of TRPV2, and were also abolished when extracellular Ca2+ was removed. Taken together this indicates functional TRPV2 channels in peritubular cells. When applied for 24 to 48 h, CBD induced expression of proinflammatory factors. In particular, mRNA and secreted protein levels of the proinflammatory chemokine interleukin-8 (IL-8/CXCL8) were elevated. Via its known roles as a major mediator of the inflammatory response and as an angiogenic factor, this chemokine may play a role in testicular physiology and pathology.

Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia

2016 ◽  
Vol 21 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Takefumi Kamakura ◽  
Makoto Kondo ◽  
Yoshihisa Koyama ◽  
Yukiko Hanada ◽  
Yusuke Ishida ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Trigeminal Ganglia ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv Channels ◽  
Polymerase Chain ◽  
Transient Receptor

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.

An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes

2009 ◽  
Vol 297 (5) ◽  
pp. C1082-C1090 ◽  
Author(s):  
Yuka Itoh ◽  
Noriyuki Hatano ◽  
Hidetoshi Hayashi ◽  
Kikuo Onozaki ◽  
Keiji Miyazawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Level ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Ruthenium Red ◽  
Intracellular Ca ◽  
Environmental Sensor ◽  
Significant Expression ◽  
Transient Receptor

The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation of intracellular Ca2+ (Ca2+i) in several types of cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is a functional regulator of Ca2+i in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4α-phorbol 12,13-didecanoate (4αPDD) effectively elevated Ca2+i in the RA and CTR cells, which was abolished by the removal of external Ca2+. Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with human TRPV4 (MH7A-V4), 4αPDD elevated the Ca2+i in a similar manner to those in the RA and CTR cells. Electrophysiological analysis also revealed that 4αPDD activated nonselective cationic currents in RA cells. Application of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca2+i, but this does not occur when it was applied to MH7A cells. Treatment of RA but not MH7A cells with 4αPDD for 24 h reduced their production of IL-8. These results suggest that an environmental sensor, TRPV4, is a novel regulator of intracellular Ca2+ in human synoviocytes.

scholarly journals Transient Receptor Potential Vanilloid 5 Mediates Ca2+ Influx and Inhibits Chondrocyte Autophagy in a Rat Osteoarthritis Model

2017 ◽  
Vol 42 (1) ◽  
pp. 319-332 ◽  
Author(s):  
Yingliang Wei ◽  
Yanfang Wang ◽  
Yutong Wang ◽  
Lunhao Bai
Keyword(s):  
Articular Cartilage ◽  
Transient Receptor Potential ◽  
Joint Destruction ◽  
Receptor Potential ◽  
B Cell Lymphoma ◽  
Transient Receptor Potential Channel ◽  
Ruthenium Red ◽  
Protective Mechanism ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Background: Autophagy, a self-protective mechanism of chondrocytes, has become a promising target to impede the progress of osteoarthritis (OA). Autophagy is regulated by cytosolic Ca2+ activity and may thus be modified by the Ca2+ permeable transient receptor potential channel vanilloid 5 (TRPV5). Therefore, we investigated the potential role of TRPV5 in mediating Ca2+ influx and in inhibiting chondrocyte autophagy in a rat OA model. Methods: The rat OA model was assessed by macroscopic and histological analyses. light chain 3B (LC3B) immunolocalization was detected by immunohistochemistry. TRPV5, LC3B and calmodulin in OA articular cartilage were assessed by real time polymerase chain reaction (RT-PCR) and western blotting. TRPV5 small interfering RNA (TRPV5 siRNA) were transfected into rat primary chondrocyte then the calmodulin and LC3B was detected by immunofluorescence. The functionality of the TRPV5 was assessed by Ca2+ influx. Western blot was used to measure autophagy-related proteins. Results: We constructed a monosodium iodoacetate (MIA) -induced rat OA model and found that ruthenium red (TRPV5 inhibitor) slowed the progression of joint destruction. We found that the TRPV5 and calmodulin were up-regulated but LC3B was down-regulated in articular cartilage following prolonged progression of OA. Furthermore, the up-regulated TRPV5 channel caused an increase in the Ca2+ influx in chondrocytes. The up-regulation of TRPV5 stimulated Ca2+ influx, which inhibited autophagy by increasing the production of calmodulin, phosphorylation of calmodulin dependent protein kinases II (p-CAMK II), phosphorylation of Beclin1 (p-Beclin1), and protein of B-cell lymphoma-2 (Bcl-2), and attenuating ratio of LC3-II/ LC3-. Conclusion: Up-regulated TRPV5 as an initiating factor inhibited chondrocyte autophagy via the mediation of Ca2+ influx.

scholarly journals 8-Bromo-cyclic inosine diphosphoribose: towards a selective cyclic ADP-ribose agonist

2009 ◽  
Vol 422 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Tanja Kirchberger ◽  
Christelle Moreau ◽  
Gerd K. Wagner ◽  
Ralf Fliegert ◽  
Cornelia C. Siebrands ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Direct Analysis ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Store Depletion ◽  
293 Cells ◽  
Cyclic Adp Ribose ◽  
T Lymphoma ◽  
Transient Receptor

cADPR (cyclic ADP-ribose) is a universal Ca2+ mobilizing second messenger. In T-cells cADPR is involved in sustained Ca2+ release and also in Ca2+ entry. Potential mechanisms for the latter include either capacitative Ca2+ entry, secondary to store depletion by cADPR, or direct activation of the non-selective cation channel TRPM2 (transient receptor potential cation channel, subfamily melastatin, member 2). Here we characterize the molecular target of the newly-described membrane-permeant cADPR agonist 8-Br-N1-cIDPR (8-bromo-cyclic IDP-ribose). 8-Br-N1-cIDPR evoked Ca2+ signalling in the human T-lymphoma cell line Jurkat and in primary rat T-lymphocytes. Ca2+ signalling induced by 8-Br-N1-cIDPR consisted of Ca2+ release and Ca2+ entry. Whereas Ca2+ release was sensitive to both the RyR (ryanodine receptor) blocker RuRed (Ruthenium Red) and the cADPR antagonist 8-Br-cADPR (8-bromo-cyclic ADP-ribose), Ca2+ entry was inhibited by the Ca2+ entry blockers Gd3+ (gadolinium ion) and SKF-96365, as well as by 8-Br-cADPR. To unravel a potential role for TRPM2 in sustained Ca2+ entry evoked by 8-Br-N1-cIDPR, TRPM2 was overexpressed in HEK (human embryonic kidney)-293 cells. However, though activation by H2O2 was enhanced dramatically in those cells, Ca2+ signalling induced by 8-Br-N1-cIDPR was almost unaffected. Similarly, direct analysis of TRPM2 currents did not reveal activation or co-activation of TRPM2 by 8-Br-N1-cIDPR. In summary, the sensitivity to the Ca2+ entry blockers Gd3+ and SKF-96365 is in favour of the concept of capacitative Ca2+ entry, secondary to store depletion by 8-Br-N1-cIDPR. Taken together, 8-Br-N1-cIDPR appears to be the first cADPR agonist affecting Ca2+ release and secondary Ca2+ entry, but without effect on TRPM2.

scholarly journals Generators of Pressure-Evoked Currents in Vertebrate Outer Retinal Neurons

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1288
Author(s):  
Ji-Jie Pang ◽  
Fan Gao ◽  
Samuel M. Wu
Keyword(s):  
Transient Receptor Potential ◽  
Peripheral Vision ◽  
Plexiform Layer ◽  
Outward Current ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Ruthenium Red ◽  
K Channel ◽  
Photoreceptor Outer Segment ◽  
The Impact

(1) Background: High-tension glaucoma damages the peripheral vision dominated by rods. How mechanosensitive channels (MSCs) in the outer retina mediate pressure responses is unclear. (2) Methods: Immunocytochemistry, patch clamp, and channel fluorescence were used to study MSCs in salamander photoreceptors. (3) Results: Immunoreactivity of transient receptor potential channel vanilloid 4 (TRPV4) was revealed in the outer plexiform layer, K+ channel TRAAK in the photoreceptor outer segment (OS), and TRPV2 in some rod OS disks. Pressure on the rod inner segment evoked sustained currents of three components: A) the inward current at <−50 mV (Ipi), sensitive to Co2+; B) leak outward current at ³−80 mV (Ipo), sensitive to intracellular Cs+ and ruthenium red; and C) cation current reversed at ~10 mV (Ipc). Hypotonicity induced slow currents like Ipc. Environmental pressure and light increased the FM 1-43-identified open MSCs in the OS membrane, while pressure on the OS with internal Cs+ closed a Ca2+-dependent current reversed at ~0 mV. Rod photocurrents were thermosensitive and affected by MSC blockers. (4) Conclusions: Rods possess depolarizing (TRPV) and hyperpolarizing (K+) MSCs, which mediate mutually compensating currents between −50 mV and 10 mV, serve as an electrical cushion to minimize the impact of ocular mechanical stress.

scholarly journals The Presence of Colony-Stimulating Factor-1 and Its Receptor in Different Cells of the Testis; It Involved in the Development of Spermatogenesis In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2325
Author(s):  
Alaa Sawaied ◽  
Eden Arazi ◽  
Ahmad AbuElhija ◽  
Eitan Lunenfeld ◽  
Mahmoud Huleihel
Keyword(s):  
Testicular Tissue ◽  
Culture Conditions ◽  
Human Testis ◽  
Seminiferous Tubules ◽  
Colony Stimulating Factor ◽  
Protein Levels ◽  
Stimulating Factor ◽  
Peritubular Cells ◽  
Testicular Macrophages

Spermatogenesis is a complex process, in which spermatogonial cells proliferate and differentiate in the seminiferous tubules of the testis to generate sperm. This process is under the regulation of endocrine and testicular paracrine/autocrine factors. In the present study, we demonstrated that colony stimulating factor-1 (CSF-1) is produced by mouse testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells (such as CDH1-positively stained cells; a marker of spermatogonial cells). In addition, we demonstrated the presence of CSF-1 and its receptor (CSF-1R) in testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells of human testis. We also show that the protein levels of CSF-1 were the highest in testis of 1-week-old mice and significantly decreased with age (2–12-week-old). However, the transcriptome levels of CSF-1 significantly increased in 2–3-week-old compared to 1-week-old, and thereafter significantly decreased with age. On the other hand, the transcriptome levels of CSF-1R was significantly higher in mouse testicular tissue of all examined ages (2–12-week-old) compared to 1-week-old. Our results demonstrate the involvement of CSF-1 in the induction the proliferation and differentiation of spermatogonial cells to meiotic and postmeiotic stages (BOULE- and ACROSIN-positive cells) under in vitro culture conditions, using methylcellulose culture system (MCS). Thus, it is possible to suggest that CSF-1 system, as a testicular paracrine/autocrine system, is involved in the development of different stages of spermatogenesis and may be used in the development of future therapeutic strategies for treatment of male infertility.

Stretch-activated cation channel TRPV4 mediates hyposmotically induced prolactin release from prolactin cells of mozambique tilapia Oreochromis mossambicus

2012 ◽  
Vol 302 (8) ◽  
pp. R1004-R1011 ◽  
Author(s):  
Soichi Watanabe ◽  
Andre P. Seale ◽  
E. Gordon Grau ◽  
Toyoji Kaneko
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Immunohistochemical Analysis ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Transient Receptor Potential Vanilloid ◽  
Functional Assay ◽  
Mozambique Tilapia ◽  
Transient Receptor ◽  
Rostral Pars Distalis

In teleost fish, prolactin (PRL) is an important hormone for hyperosmoregulation. The release of PRL from the pituitary of Mozambique tilapia is stimulated by a decrease in extracellular osmolality. Previous studies have shown that hyposmotically induced PRL release is linked with cell volume changes, and that stretch-activated Ca2+ channels are likely responsible for the initiation of the signal transduction for PRL release. In this study, we identified the stretch-activated Ca2+ channel transient receptor potential vanilloid 4 (TRPV4) from the rostral pars distalis (RPD) of tilapia acclimated to freshwater (FW). TRPV4 transcripts were ubiquitously expressed in tilapia; the level of expression in RPDs of FW-acclimated fish was lower than that found in RPDs of seawater (SW)-acclimated fish. Immunohistochemical analysis of the pituitary revealed that TRPV4 is localized in the cell membrane of PRL cells of both FW and SW tilapia. A functional assay with CHO-K1 cells showed that tilapia TRPV4 responded to a decrease in extracellular osmolality, and that its function was suppressed by ruthenium red (RR) and activated by 4α-phorbol 12,13-didecanoate (4aPDD). Exposure of dissociated PRL cells from FW-acclimated tilapia to RR blocked hyposmolality induced PRL release. PRL release, on the other hand, was stimulated by 4aPDD. These results indicate that PRL release in response to physiologically relevant changes in extracellular osmolality is mediated by the osmotically sensitive TRPV4 cation channel.

scholarly journals Activation of the Cation Channel Long Transient Receptor Potential Channel 2 (LTRPC2) by Hydrogen Peroxide

2002 ◽  
Vol 277 (26) ◽  
pp. 23150-23156 ◽  
Author(s):  
Edith Wehage ◽  
Jörg Eisfeld ◽  
Inka Heiner ◽  
Eberhard Jüngling ◽  
Christof Zitt ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Cation Channel ◽  
Transient Receptor

scholarly journals FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3

2013 ◽  
Vol 20 (3) ◽  
pp. 415-429 ◽  
Author(s):  
Xiang Tao ◽  
Naiqing Zhao ◽  
Hongyan Jin ◽  
Zhenbo Zhang ◽  
Yintao Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Transient Receptor Potential ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Ovarian Cancer Cells ◽  
Protein Levels ◽  
Transient Receptor

Recent studies have suggested that FSH plays an important role in ovarian epithelial carcinogenesis. We demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis and facilitates neovascularisation. Our previous work has shown that transient receptor potential channel C3 (TRPC3) contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between FSH and TRPC3. We found that FSH stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. siRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and blocked apoptosis in ovarian cancer cell lines. FSH stimulation was associated with the up-regulation of TRPC3, while also facilitating the influx of Ca2+ after treatment with a TRPC-specific agonist. Knockdown of TRPC3 abrogated FSH-stimulated Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1-α and VEGF. Ovarian cancer specimens were analysed for TRPC3 expression; higher TRPC3 expression levels correlated with early relapse and worse prognosis. Association with poor disease-free survival and overall survival remained after adjusting for clinical stage and grade. In conclusion, TRPC3 plays a significant role in the stimulating activity of FSH and could be a potential therapeutic target for the treatment of ovarian cancer, particularly in postmenopausal women with elevated FSH levels.

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