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  1. Article ; Online: Role of the TRPV Channels in the Endoplasmic Reticulum Calcium Homeostasis

    Aurélien Haustrate / Natalia Prevarskaya / V’yacheslav Lehen’kyi

    Cells, Vol 9, Iss 2, p

    2020  Volume 317

    Abstract: It has been widely established that transient receptor potential vanilloid (TRPV) channels play a crucial role in calcium homeostasis in mammalian cells. Modulation of TRPV channels activity can modify their physiological function leading to some ... ...

    Abstract It has been widely established that transient receptor potential vanilloid (TRPV) channels play a crucial role in calcium homeostasis in mammalian cells. Modulation of TRPV channels activity can modify their physiological function leading to some diseases and disorders like neurodegeneration, pain, cancer, skin disorders, etc. It should be noted that, despite TRPV channels importance, our knowledge of the TRPV channels functions in cells is mostly limited to their plasma membrane location. However, some TRPV channels were shown to be expressed in the endoplasmic reticulum where their modulation by activators and/or inhibitors was demonstrated to be crucial for intracellular signaling. In this review, we have intended to summarize the poorly studied roles and functions of these channels in the endoplasmic reticulum.
    Keywords trpv channels ; endoplasmic reticulum ; calcium signaling ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

    Gonçalo Mesquita / Natalia Prevarskaya / Albrecht Schwab / V’yacheslav Lehen’kyi

    Cells, Vol 10, Iss 1021, p

    2021  Volume 1021

    Abstract: The transient receptor potential channels (TRPs) have been related to several different physiologies that range from a role in sensory physiology (including thermo- and osmosensation) to a role in some pathologies like cancer. The great diversity of ... ...

    Abstract The transient receptor potential channels (TRPs) have been related to several different physiologies that range from a role in sensory physiology (including thermo- and osmosensation) to a role in some pathologies like cancer. The great diversity of functions performed by these channels is represented by nine sub-families that constitute the TRP channel superfamily. From the mid-2000s, several reports have shown the potential role of the TRP channels in cancers of multiple origin. The pancreatic cancer is one of the deadliest cancers worldwide. Its prevalence is predicted to rise further. Disappointingly, the treatments currently used are ineffective. There is an urgency to find new ways to counter this disease and one of the answers may lie in the ion channels belonging to the superfamily of TRP channels. In this review, we analyse the existing knowledge on the role of TRP channels in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The functions of these channels in other cancers are also considered. This might be of interest for an extrapolation to the pancreatic cancer in an attempt to identify potential therapeutic interventions.
    Keywords ion channels ; TRP channels ; pancreatic ductal adenocarcinoma ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A Novel Anti-TRPV6 Antibody and Its Application in Cancer Diagnosis In Vitro

    Aurélien Haustrate / Adriana Mihalache / Clément Cordier / Pierre Gosset / Natalia Prevarskaya / V’yacheslav Lehen’kyi

    International Journal of Molecular Sciences, Vol 24, Iss 1, p

    2022  Volume 419

    Abstract: Though the first discovery of TRPV6 channel expression in various tissues took place in the early 2000s, reliable tools for its protein detection in various cells and tissues are still missing. Here we show the generation and validation of rabbit ... ...

    Abstract Though the first discovery of TRPV6 channel expression in various tissues took place in the early 2000s, reliable tools for its protein detection in various cells and tissues are still missing. Here we show the generation and validation of rabbit polyclonal anti-TRPV6 channel antibodies (rb79–82) against four epitopes of 15 amino acids. Among them, only one antibody, rb79, was capable of detecting the full-length glycosylated form of the TRPV6 channel at around 100 kDa. The generated antibody was shown to be suitable for all in vitro applications, such as immunoblotting, immunoprecipitation, immunocytochemistry, immunofluorescence, etc. One of the most important applications is immunohistochemistry using the paraffin-embedded sections from cancer resection specimens. Using prostate cancer resection specimens, we have confirmed the absence of the TRPV6 protein in both healthy and benign hyperplasia, as well as its expression and correlation to the prostate cancer grades. Thus, the generated rabbit polyclonal anti-TRPV6 channel antibody rb79 is suitable for all in vitro diagnostic applications and particularly for the diagnosis in clinics using paraffin-embedded sections from patients suffering from various diseases and disorders involving the TRPV6 channel.
    Keywords antibody ; TRPV6 channel ; diagnostic ; immunoblotting ; immunohistochemistry ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: TRPM Family Channels in Cancer

    Aline Hantute-Ghesquier / Aurélien Haustrate / Natalia Prevarskaya / V’yacheslav Lehen’kyi

    Pharmaceuticals, Vol 11, Iss 2, p

    2018  Volume 58

    Abstract: Members of the TRPM (“Melastatin”) family fall into the subclass of the TRP channels having varying permeability to Ca2+ and Mg2+, with three members of the TRPM family being chanzymes, which contain C-terminal enzyme domains. The role of different TRPM ... ...

    Abstract Members of the TRPM (“Melastatin”) family fall into the subclass of the TRP channels having varying permeability to Ca2+ and Mg2+, with three members of the TRPM family being chanzymes, which contain C-terminal enzyme domains. The role of different TRPM members has been shown in various cancers such as prostate cancer for mostly TRPM8 and TRPM2, breast cancer for mostly TRPM2 and TRPM7, and pancreatic cancer for TRPM2/7/8 channels. The role of TRPM5 channels has been shown in lung cancer, TRPM1 in melanoma, and TRPM4 channel in prostate cancer as well. Thus, the TRPM family of channels may represent an appealing target for the anticancer therapy.
    Keywords TRPM channels ; cancer ; target ; therapy ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Interaction of Human α-1-Acid Glycoprotein (AGP) with Citrate-Stabilized Gold Nanoparticles: Formation of Unexpectedly Strong Binding Events

    Mohammadi, Fakhrossadat / Amin Sahraei / Chengnan Li / Aurélien Haustrate / V’yacheslav Lehen’kyi / Alexandre Barras / Rabah Boukherroub / Sabine Szunerits

    Journal of physical chemistry. 2019 Feb. 18, v. 123, no. 8

    2019  

    Abstract: Numerous studies have investigated the interaction of high-abundance plasma proteins with different nanostructures. In this work, we focus on the interaction of citrate-stabilized spherical gold nanoparticles (Au-CIT) with human α-1-acid glycoprotein ( ... ...

    Abstract Numerous studies have investigated the interaction of high-abundance plasma proteins with different nanostructures. In this work, we focus on the interaction of citrate-stabilized spherical gold nanoparticles (Au-CIT) with human α-1-acid glycoprotein (AGP), one of the major acute phase proteins in humans with a normal plasma concentration between 0.6 and 1.2 mg mL–¹, which can increase 4-fold in response to systemic tissue injury, inflammation, or infection. It is shown using different physicochemical approaches that AGP interaction not only takes place readily on Au-CIT nanoparticles, but the binding constant is as high as 10¹² M–¹, being several orders of magnitude larger than other highly abundant serum proteins. The adsorbed AGP preserved its biological identity and the formed Au-CIT/AGP particles were nontoxic to cells over a large concentration range. This is in contrast to positively charged gold nanostructures, which displayed lower binding affinity to AGP and higher cytotoxicity even at low particle concentrations. The in vivo investigations showed that the Au-CIT/AGP particles are mostly distributed in the liver and spleen and are absent in kidney and bladder as well as in peripheral organs like brain, confirming their confinement to the blood vessels.
    Keywords acute phase proteins ; binding capacity ; bladder ; blood vessels ; brain ; cytotoxicity ; glycoproteins ; gold ; humans ; inflammation ; kidneys ; liver ; nanogold ; nanoparticles ; physical chemistry ; spleen
    Language English
    Dates of publication 2019-0218
    Size p. 5073-5083.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1932-7455
    DOI 10.1021/acs.jpcc.8b10455
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

    Agathe Oulidi / Alexandre Bokhobza / Dimitra Gkika / Fabien Vanden Abeele / V'yacheslav Lehen'kyi / L'houcine Ouafik / Brigitte Mauroy / Natalia Prevarskaya

    PLoS ONE, Vol 8, Iss 5, p e

    2013  Volume 64885

    Abstract: Adrenomedullin (AM) is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer ... ...

    Abstract Adrenomedullin (AM) is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Cytoskeleton reorganization as an alternative mechanism of store-operated calcium entry control in neuroendocrine-differentiated cells.

    Karine Vanoverberghe / V'yacheslav Lehen'kyi / Stéphanie Thébault / Maylis Raphaël / Fabien Vanden Abeele / Christian Slomianny / Pascal Mariot / Natalia Prevarskaya

    PLoS ONE, Vol 7, Iss 9, p e

    2012  Volume 45615

    Abstract: Neuroendocrine differentiation (NED) is a hallmark of advanced androgen-independent prostate cancer, for which no successful therapy exists. NED tumour cells escape apoptotic cell death by alterations of Ca(2+) homeostasis where the store-operated Ca(2+) ...

    Abstract Neuroendocrine differentiation (NED) is a hallmark of advanced androgen-independent prostate cancer, for which no successful therapy exists. NED tumour cells escape apoptotic cell death by alterations of Ca(2+) homeostasis where the store-operated Ca(2+) entry (SOCE) is known to be a key event. We have previously shown that the downregulation of Orai1 protein representing the major molecular component of endogenous SOCE in human prostate cancer cells, and constituting the principal source of Ca(2+) influx used by the cell to trigger apoptosis, contributes to the establishment of an apoptosis-resistant phenotype (Cell Death Dis. 2010 Sep 16;1:e75.). Here, we report for the first time that the decrease of SOCE during NED may be caused by alternative NED-induced mechanism involving cytoskeleton reorganisation. NED induced by androgen deprivation resulted in a decrease of SOCE due to cortical F-actin over-polymerization which inhibits thapsigargin-induced SOCE. The disruption of F-actin polymerization by Cytochalasin D in NED cells restored SOCE, while the induction of F-actin polymerization by jasplakinolide or calyculin A diminished SOCE without changing the expression of key SOCE players: Orai1, STIM1, and TRPC1. Our data suggest that targeting cytoskeleton-induced pathways of malignant cells together with SOCE-involved channels may prove a useful strategy in the treatment of advanced prostate cancer.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.

    V'yacheslav Lehen'kyi / Maylis Raphaël / Agathe Oulidi / Matthieu Flourakis / Sergii Khalimonchyk / Artem Kondratskyi / Dmitri V Gordienko / Brigitte Mauroy / Jean-Lois Bonnal / Roman Skryma / Natalia Prevarskaya

    PLoS ONE, Vol 6, Iss 2, p e

    2011  Volume 16856

    Abstract: Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high ... ...

    Abstract Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enhances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2011-02-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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