Search results for "organic cation transporter"
showing 10 items of 11 documents
Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules.
1998
AbstractChromosome 11p15.5 harbors a gene or genes involved in Beckwith-Wiedemann syndrome that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins. In this report, we have investigated the transport properties of ORCTL2 and show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry analyses performed with anti-ORCTL2 polyc.onal antibod…
Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4α upregulation in primary human hepatocytes
2013
Abstract Background Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4α (HNF4α). HNF4α expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. Methods It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4α up-regulation in primary human hepatocytes.We also examined which other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexa…
Caki-1 cells as a model system for the interaction of renally secreted drugs with OCT3.
2008
<i>Background/Aims:</i> Organic cation transporters (OCT) in the proximal tubules (PTs) participate in the renal secretion of several therapeutic agents. The exact role of OCT3 in renal secretion remains undetermined, partially due to the lack of an appropriate in vitro model system. The current work introduces the PT representative cell line, Caki-1, as a model system for studying the involvement of OCT3 in renal secretion. <i>Methods:</i> Caki-1 cells were characterized for OCT3 expression via real-time RT-PCR and immunocytochemical staining techniques. Uptake kinetics of OCT3 in Caki-1 cells was determined using prototypical substrates and inhibitors. Inhibition o…
Downregulation of organic cation transporter 1 (SLC22A1) is associated with tumor progression and reduced patient survival in human cholangiocellular…
2013
Cholangiocellular carcinoma (CCA) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCA patients is very poor and conventional chemotherapy has been proven ineffective in improving long‑term patient survival rates. Organic cation transporters (OCTs) mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are considered responsible for the responsiveness towards platinum‑based chemotherapies. Currently, there are no data available regarding the role of OCTs in CCA. Therefore, the aim of this study was to investigate the expression of OCT1 and OCT3 in CCA and the corresponding non-neoplastic tumor‑su…
Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules.
2016
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Forster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells. Studies with CD63-knockout mice indicate that in renal proximal tubules, CD63 determines the insertion of the mouse ortholog…
Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
2019
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 (SLC22A1/hOCT1) and hOCT2 (SLC22A2/hOCT2) are highly expressed in hepatic (hOCT1) and in renal and neuronal tissue (hOCT2), suggesting a possible role in modulating neurotransmitter activity in the liver, kidney, and brain, and their clearance from the blood. Even though there are several data demonstrating that OCTs are regulated under various patho-physiological conditions, it remains largely unknown which proteins directly interact with OCTs and thereby influence …
Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance
2012
Abstract Background Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC). Methods OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by…
Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis
2017
// Johanna Vollmar 1 , Anja Lautem 2 , Ellen Closs 3 , Detlef Schuppan 4 , Yong Ook Kim 4 , Daniel Grimm 1 , Jens U. Marquardt 1 , Peter Fuchs 1 , Beate K. Straub 5 , Arno Schad 5 , Dirk Grundemann 6 , Jorn M. Schattenberg 1 , Nadine Gehrke 1 , Marcus A. Worns 1 , Jan Baumgart 7 , Peter R. Galle 1 and Tim Zimmermann 1 1 Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 2 Department of Hepatobiliary and Transplantation Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 3 Department of Pharmacology, University Medical Center, Johannes Gutenberg-University Mainz, …
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
2020
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…
Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the Europe…
2020
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…