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  1. Article ; Online: Role of Organic Cation Transporter 2 in Autophagy Induced by Platinum Derivatives.

    Eltayeb, Sara Ahmed / Ciarimboli, Giuliano / Beul, Katrin / Seno Di Marco, Giovana / Barz, Vivien

    International journal of molecular sciences

    2022  Volume 23, Issue 3

    Abstract: The human organic cation transporter 2 (hOCT2) mediates renal and neuronal cellular cisplatin and oxaliplatin uptake, and therefore plays a significant role in the development of side effects associated with these chemotherapeutic drugs. Autophagy is ... ...

    Abstract The human organic cation transporter 2 (hOCT2) mediates renal and neuronal cellular cisplatin and oxaliplatin uptake, and therefore plays a significant role in the development of side effects associated with these chemotherapeutic drugs. Autophagy is induced by cisplatin and oxaliplatin treatment and is believed to promote cell survival under stressful conditions. We examined in vitro the role of hOCT2 on autophagy induced by cisplatin and oxaliplatin. We also explored the effect of autophagy on toxicities of these platinum derivatives. Our results indicate that autophagy, measured as LC3 II accumulation and reduction in p62 expression level, is induced in response to cisplatin and oxaliplatin in HEK293-hOCT2 but not in wild-type HEK293 cells. Furthermore, inhibition of autophagy is associated with higher toxicity of platinum derivatives, and starvation was found to offer protection against cisplatin-associated toxicity. In conclusion, activation of autophagy could be a potential strategy to protect against unwanted toxicities induced by treatment with platinum derivatives.
    MeSH term(s) Autophagy ; Biomarkers/metabolism ; Cisplatin/toxicity ; Gene Expression Regulation/drug effects ; HEK293 Cells ; Humans ; Microtubule-Associated Proteins/metabolism ; Mutation ; Organic Cation Transporter 2/genetics ; Oxaliplatin/toxicity ; Platinum/toxicity ; Sequestosome-1 Protein/metabolism
    Chemical Substances Biomarkers ; MAP1LC3A protein, human ; Microtubule-Associated Proteins ; Organic Cation Transporter 2 ; SLC22A2 protein, human ; SQSTM1 protein, human ; Sequestosome-1 Protein ; Oxaliplatin (04ZR38536J) ; Platinum (49DFR088MY) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2022-01-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23031090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Fast simultaneous quantification of gabapentin and cetirizine in cell lysates by means of HPLC-MS/MS.

    Schlatt, Lukas / Costa, Ana Carolina Conchon / Barz, Vivien / Ciarimboli, Giuliano / Karst, Uwe

    Journal of pharmaceutical and biomedical analysis

    2020  Volume 184, Page(s) 113172

    Abstract: A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was successfully developed for the simultaneous detection of gabapentin (GBP) and cetirizine (CTZ) in cell lysates. Multiple reaction monitoring (MRM) transitions were ... ...

    Abstract A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was successfully developed for the simultaneous detection of gabapentin (GBP) and cetirizine (CTZ) in cell lysates. Multiple reaction monitoring (MRM) transitions were found for GBP, CTZ and deuterated internal standards of both, allowing a selective and sensitive detection. Limits of detection (LODs) of 0.04 ng/mL and 0.07 ng/mL were achieved for CTZ and GBP respectively, and a linear range could be confirmed to the highest tested concentration of 50 ng/mL. Furthermore, with a total runtime of 2.5 min, this method allows a high throughput analysis. The applicability of the method was demonstrated by using it for the quantification of CTZ and GBP in cell lysates to examine the effects of renal transporters on these two analytes.
    MeSH term(s) Cetirizine/chemistry ; Chromatography, High Pressure Liquid/methods ; Gabapentin/chemistry ; Limit of Detection ; Reproducibility of Results ; Tandem Mass Spectrometry/methods
    Chemical Substances Gabapentin (6CW7F3G59X) ; Cetirizine (YO7261ME24)
    Language English
    Publishing date 2020-02-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2020.113172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rapid Regulation of Human Multidrug and Extrusion Transporters hMATE1 and hMATE2K.

    Kantauskaitė, Marta / Hucke, Anna / Reike, Moritz / Ahmed Eltayeb, Sara / Xiao, Chuyan / Barz, Vivien / Ciarimboli, Giuliano

    International journal of molecular sciences

    2020  Volume 21, Issue 14

    Abstract: Vectorial transport of organic cations (OCs) in renal proximal tubules is mediated by sequential action of human OC transporter 2 (hOCT2) and human multidrug and toxic extrusion protein 1 and 2K (hMATE1 and hMATE2K), expressed in the basolateral (hOCT2) ... ...

    Abstract Vectorial transport of organic cations (OCs) in renal proximal tubules is mediated by sequential action of human OC transporter 2 (hOCT2) and human multidrug and toxic extrusion protein 1 and 2K (hMATE1 and hMATE2K), expressed in the basolateral (hOCT2) and luminal (hMATE1 and hMATE2K) plasma membranes, respectively. It is well known that hOCT2 activity is subjected to rapid regulation by several signaling pathways, suggesting that renal OC secretion may be acutely adapted to physiological requirements. Therefore, in this work, the acute regulation of hMATEs stably expressed in human embryonic kidney cells was characterized using the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP
    MeSH term(s) Animals ; Biological Transport/drug effects ; Biological Transport/genetics ; Casein Kinase II/antagonists & inhibitors ; Cations/metabolism ; Cimetidine/pharmacology ; Dogs ; Fluorescence ; Fluorescent Dyes/metabolism ; Guanidines/pharmacology ; HEK293 Cells ; Humans ; Kidney/metabolism ; Madin Darby Canine Kidney Cells ; Organic Cation Transport Proteins/antagonists & inhibitors ; Organic Cation Transport Proteins/genetics ; Organic Cation Transport Proteins/metabolism ; Pyridinium Compounds/metabolism ; Sodium-Hydrogen Exchanger 1/antagonists & inhibitors ; Sulfones/pharmacology
    Chemical Substances 4-(4-dimethylaminostyryl)-1-methylpyridinium ; Cations ; Fluorescent Dyes ; Guanidines ; Organic Cation Transport Proteins ; Pyridinium Compounds ; SLC47A1 protein, human ; SLC47A2 protein, human ; SLC9A1 protein, human ; Sodium-Hydrogen Exchanger 1 ; Sulfones ; cariporide (7E3392891K) ; Cimetidine (80061L1WGD) ; Casein Kinase II (EC 2.7.11.1)
    Language English
    Publishing date 2020-07-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21145157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Notch Signaling Activity Determines Uptake and Biological Effect of Imatinib in Systemic Sclerosis Dermal Fibroblasts.

    Harrach, Saliha / Barz, Vivien / Pap, Thomas / Pavenstädt, Hermann / Schlatter, Eberhard / Edemir, Bayram / Distler, Jörg / Ciarimboli, Giuliano / Bertrand, Jessica

    The Journal of investigative dermatology

    2018  Volume 139, Issue 2, Page(s) 439–447

    Abstract: Tyrosine kinase inhibitors have emerged as a therapeutic option for rheumatic diseases such as systemic sclerosis (SSc). Because tyrosine kinases like c-Abl kinase are important for fibroblast activation and fibrosis development in SSc, the c-Abl ... ...

    Abstract Tyrosine kinase inhibitors have emerged as a therapeutic option for rheumatic diseases such as systemic sclerosis (SSc). Because tyrosine kinases like c-Abl kinase are important for fibroblast activation and fibrosis development in SSc, the c-Abl inhibitor imatinib was proposed for SSc treatment. Transporters for organic cations have become increasingly recognized as an important determinant for uptake and efficacy of tyrosine kinase inhibitors. Therefore, we investigated the role of organic cation transporters in the uptake of imatinib. Moreover, the influence of important SSc pathogenetic factors, like PDGF and Notch pathway activation on these uptake processes, has been studied. We showed that organic cation transporters OCT1-3, novel organic cation transporters OCTN1/2, and the multidrug and toxin extrusion protein MATE1 are expressed in healthy dermal and SSc fibroblasts. Decreased expression levels of MATE1 and decreased imatinib uptake were measured in SSc fibroblasts. In small interfering RNA experiments, MATE1 was identified as key transporter for imatinib uptake and biological effect in dermal fibroblasts. Furthermore, PDGF reduced imatinib uptake by decreasing MATE1 expression in SSc fibroblasts, but not in healthy fibroblasts. Blocking the Notch pathway in SSc fibroblasts increased MATE1 transporter expression and imatinib uptake. In conclusion, MATE1-mediated transport governs therapeutic efficacy of imatinib in SSc.
    MeSH term(s) Biopsy ; Cells, Cultured ; Dermis/cytology ; Dermis/metabolism ; Dermis/pathology ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; Humans ; Imatinib Mesylate/pharmacokinetics ; Imatinib Mesylate/therapeutic use ; Organic Cation Transport Proteins/genetics ; Organic Cation Transport Proteins/metabolism ; Platelet-Derived Growth Factor/metabolism ; Primary Cell Culture ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/therapeutic use ; RNA, Small Interfering/metabolism ; Receptors, Notch/metabolism ; Scleroderma, Systemic/drug therapy ; Scleroderma, Systemic/pathology ; Signal Transduction
    Chemical Substances Organic Cation Transport Proteins ; Platelet-Derived Growth Factor ; Protein Kinase Inhibitors ; RNA, Small Interfering ; Receptors, Notch ; SLC47A1 protein, human ; Imatinib Mesylate (8A1O1M485B)
    Language English
    Publishing date 2018-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2018.08.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ui VI Zs.124: Show issues Location:
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  5. Article ; Online: Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.

    Costa, Ana Carolina Conchon / Yamamoto, Priscila Akemi / Lauretti, Gabriela Rocha / de Lima Benzi, Jhohann Richard / Zanelli, Cleslei Fernando / Barz, Vivien / Ciarimboli, Giuliano / de Moraes, Natália Valadares

    Journal of clinical pharmacology

    2020  Volume 60, Issue 8, Page(s) 1076–1086

    Abstract: Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug-drug interaction between GBP and cetirizine ( ... ...

    Abstract Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug-drug interaction between GBP and cetirizine (CTZ), an inhibitor of transporters for organic cations. An open-label, 2-period, crossover, nonrandomized clinical trial was conducted in patients with neuropathic pain to evaluate the effect of CTZ on GBP pharmacokinetics. Twelve participants were treated with a single dose of 300 mg GBP (treatment A) or with 20 mg/d of CTZ for 5 days and 300 mg GBP on the last day of CTZ treatment (treatment B). Blood sampling and pain intensity evaluation were performed up to 36 hours after GBP administration. The interaction of GBP and CTZ with transporters for organic cations was studied in human embryonic kidney (HEK) cells expressing the organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and OCTN1. CTZ treatment resulted in reduced area under the concentration-time curve and peak concentration compared with treatment A. In treatment B, the lower plasma concentrations of GBP resulted in reduced pain attenuation. GBP renal clearance was similar between treatments. GBP has low apparent affinity for OCT2 (concentration of an inhibitor where the response [or binding] is reduced by half [IC
    Language English
    Publishing date 2020-03-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 188980-1
    ISSN 1552-4604 ; 0091-2700 ; 0021-9754
    ISSN (online) 1552-4604
    ISSN 0091-2700 ; 0021-9754
    DOI 10.1002/jcph.1603
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  6. Article ; Online: Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2.

    Snieder, Beatrice / Brast, Sabine / Grabner, Alexander / Buchholz, Sven / Schröter, Rita / Spoden, Gilles A / Florin, Luise / Salomon, Johanna / Albrecht, Tobias / Barz, Vivien / Sparreboom, Alex / Ciarimboli, Giuliano

    SLAS discovery : advancing life sciences R & D

    2019  Volume 24, Issue 9, Page(s) 904–914

    Abstract: Organic cation transporters (OCTs) are membrane proteins with relevant physiological (because they accept neurotransmitters as substrate) and pharmacological (because of their interaction with drugs) roles. The human OCTs hOCT1 ( ...

    Abstract Organic cation transporters (OCTs) are membrane proteins with relevant physiological (because they accept neurotransmitters as substrate) and pharmacological (because of their interaction with drugs) roles. The human OCTs hOCT1 (
    MeSH term(s) Animals ; Cell Membrane/metabolism ; Dogs ; HEK293 Cells ; Humans ; Madin Darby Canine Kidney Cells ; Membrane Proteins/metabolism ; Octamer Transcription Factor-1/metabolism ; Organic Cation Transporter 2/metabolism ; Protein Transport/physiology ; Tetraspanin 29/metabolism ; Tetraspanins/metabolism
    Chemical Substances CD9 protein, human ; Membrane Proteins ; Octamer Transcription Factor-1 ; Organic Cation Transporter 2 ; POU2F1 protein, human ; SLC22A2 protein, human ; Tetraspanin 29 ; Tetraspanins
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555219859837
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    Zs.A 4911: Show issues Location:
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  7. Article ; Online: An integrative approach to cisplatin chronic toxicities in mice reveals importance of organic cation-transporter-dependent protein networks for renoprotection.

    Hucke, Anna / Rinschen, Markus M / Bauer, Oliver B / Sperling, Michael / Karst, Uwe / Köppen, Christina / Sommer, Karolin / Schröter, Rita / Ceresa, Cecilia / Chiorazzi, Alessia / Canta, Annalisa / Semperboni, Sara / Marmiroli, Paola / Cavaletti, Guido / Schlatt, Stefan / Schlatter, Eberhard / Pavenstädt, Hermann / Heitplatz, Barbara / Van Marck, Veerle /
    Sparreboom, Alex / Barz, Vivien / Knief, Arne / Deuster, Dirk / Zehnhoff-Dinnesen, Antoinette Am / Ciarimboli, Giuliano

    Archives of toxicology

    2019  Volume 93, Issue 10, Page(s) 2835–2848

    Abstract: Cisplatin (CDDP) is one of the most important chemotherapeutic drugs in modern oncology. However, its use is limited by severe toxicities, which impair life quality after cancer. Here, we investigated the role of organic cation transporters (OCT) in ... ...

    Abstract Cisplatin (CDDP) is one of the most important chemotherapeutic drugs in modern oncology. However, its use is limited by severe toxicities, which impair life quality after cancer. Here, we investigated the role of organic cation transporters (OCT) in mediating toxicities associated with chronic (twice the week for 4 weeks) low-dose (4 mg/kg body weight) CDDP treatment (resembling therapeutic protocols in patients) of wild-type (WT) mice and mice with OCT genetic deletion (OCT1/2
    MeSH term(s) Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/toxicity ; Cisplatin/administration & dosage ; Cisplatin/toxicity ; Kidney Diseases/chemically induced ; Kidney Diseases/genetics ; Kidney Diseases/pathology ; Male ; Mice ; Mice, Knockout ; Neurotoxicity Syndromes/etiology ; Neurotoxicity Syndromes/genetics ; Octamer Transcription Factor-1/genetics ; Octamer Transcription Factor-1/metabolism ; Organic Cation Transporter 2/genetics ; Organic Cation Transporter 2/metabolism ; Ototoxicity/etiology ; Ototoxicity/genetics ; Proteomics ; Signal Transduction/drug effects
    Chemical Substances Antineoplastic Agents ; Octamer Transcription Factor-1 ; Organic Cation Transporter 2 ; Pou2f1 protein, mouse ; Slc22a2 protein, mouse ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2019-09-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-019-02557-9
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