Ralf Kubitz

Summary

Affiliation: Heinrich Heine University
Country: Germany

Publications

  1. ncbi Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase
    Ralf Kubitz
    Department of Gastroenterology, Hepatology, and Infectiology, Heinrch Heine University, Duesseldorf, Germany
    Gastroenterology 126:541-53. 2004
  2. doi A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (Ntcp)
    Claudia Stross
    Dept of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Univ Clinic of the Heinrich Heine Univ of Düsseldorf, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Am J Physiol Gastrointest Liver Physiol 305:G722-30. 2013
  3. doi The bile salt export pump (BSEP) in health and disease
    Ralf Kubitz
    Medical faculty of the Heinrich Heine University of Düsseldorf, Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Dusseldorf, Germany
    Clin Res Hepatol Gastroenterol 36:536-53. 2012
  4. pmc Toponomics method for the automated quantification of membrane protein translocation
    Olga Domanova
    Fraunhofer Institute for Applied Information Technology FIT, Schloss Birlinghoven, Sankt Augustin, Germany
    BMC Bioinformatics 12:370. 2011
  5. doi Genetic variants of the bile salt export pump: inducers and modifiers of liver diseases
    Ralf Kubitz
    Department of Gastroenterology, Hepatology and Infectiology, University Hospital Dusseldorf, Dusseldorf, Germany
    Dig Dis 29:89-92. 2011
  6. doi Cholestatic liver diseases from child to adult: the diversity of MDR3 disease
    R Kubitz
    Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Universitatsklinikum Dusseldorf
    Z Gastroenterol 49:728-36. 2011
  7. ncbi Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump
    Ralf Kubitz
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Dusseldorf, Germany
    J Clin Gastroenterol 40:171-5. 2006
  8. ncbi Ca2+-dependent protein kinase C isoforms induce cholestasis in rat liver
    Ralf Kubitz
    Department of Gastroenterology, Hepatology, and Infectiology, Heinrich Heine University, D 40225 Dusseldorf, Germany
    J Biol Chem 279:10323-30. 2004
  9. ncbi Protein kinase C induces endocytosis of the sodium taurocholate cotransporting polypeptide
    Claudia Stross
    Dept of Gastroenterology, Hepatology and Infectiology, Heinrich Heine Univ of Düsseldorf, Germany
    Am J Physiol Gastrointest Liver Physiol 299:G320-8. 2010
  10. doi Short-term feedback regulation of bile salt uptake by bile salts in rodent liver
    Stefanie Mühlfeld
    Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany
    Hepatology 56:2387-97. 2012

Collaborators

Detail Information

Publications30

  1. ncbi Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase
    Ralf Kubitz
    Department of Gastroenterology, Hepatology, and Infectiology, Heinrch Heine University, Duesseldorf, Germany
    Gastroenterology 126:541-53. 2004
    ..Trafficking of the bile salt export pump (BSEP) to the canalicular membrane was investigated in HepG2 cells and rat hepatocytes...
  2. doi A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (Ntcp)
    Claudia Stross
    Dept of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Univ Clinic of the Heinrich Heine Univ of Düsseldorf, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Am J Physiol Gastrointest Liver Physiol 305:G722-30. 2013
    ..Endocytic retrieval protects hepatocytes from elevated bile salt concentrations and is of special interest, because NTCP has been identified as a receptor for the hepatitis B and D virus...
  3. doi The bile salt export pump (BSEP) in health and disease
    Ralf Kubitz
    Medical faculty of the Heinrich Heine University of Düsseldorf, Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Dusseldorf, Germany
    Clin Res Hepatol Gastroenterol 36:536-53. 2012
    ..This review focuses on expression, localization, and function, short- and long-term regulation of BSEP as well as diseases association and treatment options for BSEP-associated diseases...
  4. pmc Toponomics method for the automated quantification of membrane protein translocation
    Olga Domanova
    Fraunhofer Institute for Applied Information Technology FIT, Schloss Birlinghoven, Sankt Augustin, Germany
    BMC Bioinformatics 12:370. 2011
    ..For validation, the cholestatic liver state was compared to the normal biological state...
  5. doi Genetic variants of the bile salt export pump: inducers and modifiers of liver diseases
    Ralf Kubitz
    Department of Gastroenterology, Hepatology and Infectiology, University Hospital Dusseldorf, Dusseldorf, Germany
    Dig Dis 29:89-92. 2011
    ..This association between bile acid transport and hepatitis C may be due to interference of bile acids with viral replication, interferon signaling or antiviral proteins...
  6. doi Cholestatic liver diseases from child to adult: the diversity of MDR3 disease
    R Kubitz
    Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Universitatsklinikum Dusseldorf
    Z Gastroenterol 49:728-36. 2011
    ..Even the same mutation may be associated with varying disease progression...
  7. ncbi Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump
    Ralf Kubitz
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Dusseldorf, Germany
    J Clin Gastroenterol 40:171-5. 2006
    ..It is concluded that this form of compound heterozygosity of the BSEP gene reduces the amount of BSEP protein due to protein instability or mis-targeting, which is the underlying reason for reduced bile salt excretion and cholemia...
  8. ncbi Ca2+-dependent protein kinase C isoforms induce cholestasis in rat liver
    Ralf Kubitz
    Department of Gastroenterology, Hepatology, and Infectiology, Heinrich Heine University, D 40225 Dusseldorf, Germany
    J Biol Chem 279:10323-30. 2004
    ..The data identify Ca(2+)-dependent PKC isoforms as inducers of cholestasis. This is mainly due to inhibition of taurocholate excretion involving transporter retrieval from the canalicular membrane...
  9. ncbi Protein kinase C induces endocytosis of the sodium taurocholate cotransporting polypeptide
    Claudia Stross
    Dept of Gastroenterology, Hepatology and Infectiology, Heinrich Heine Univ of Düsseldorf, Germany
    Am J Physiol Gastrointest Liver Physiol 299:G320-8. 2010
    ..In conclusion, Ca(2+)-dependent PKCs induce vesicular retrieval of Ntcp, thereby reducing bile salt uptake. This mechanism may protect hepatocytes from toxic intracellular bile salt concentrations...
  10. doi Short-term feedback regulation of bile salt uptake by bile salts in rodent liver
    Stefanie Mühlfeld
    Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany
    Hepatology 56:2387-97. 2012
    ..Phosphoinositide 3-kinase (PI3K) inhibitors had an additive effect, whereas Erk1/2 (extracellular signal activated kinase 1/2), p38MAPK, protein phosphatase 1/2A (PP1/2A), and reactive oxygen species (ROS) were not involved...
  11. ncbi Biliary transport systems: short-term regulation
    Ralf Kubitz
    Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University Dusseldorf, Germany
    Methods Enzymol 400:542-57. 2005
    ..Different techniques have been employed in studies on transporter retrieval and insertion, which are discussed in this chapter...
  12. doi Expression and function of the bile acid receptor TGR5 in Kupffer cells
    Verena Keitel
    Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Biochem Biophys Res Commun 372:78-84. 2008
    ....
  13. ncbi Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis
    Verena Keitel
    Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Heinrich Heine Universitat, Dusseldorf, Germany
    Hepatology 41:1160-72. 2005
    ..Upregulation of MRP4, but not of MRP3, might represent an important escape mechanism for bile salt extrusion in PFIC...
  14. ncbi Degradation of the sodium taurocholate cotransporting polypeptide (NTCP) by the ubiquitin-proteasome system
    Thomas Kühlkamp
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, D 40225 Dusseldorf, Germany
    Biol Chem 386:1065-74. 2005
    ..An imbalance in the synthesis and degradation of NTCP at the level of the ER or alterations in the ERAD machinery might be the cause of intracellular NTCP deposits in transient transfections and in cholestatic livers...
  15. ncbi Combined mutations of canalicular transporter proteins cause severe intrahepatic cholestasis of pregnancy
    Verena Keitel
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Gastroenterology 131:624-9. 2006
    ..Reduced bile salt secretion through BSEP may explain the persistence of elevated bile salt levels and incomplete efficacy of ursodeoxycholate treatment...
  16. ncbi A novel mutation within a transmembrane helix of the bile salt export pump (BSEP, ABCB11) with delayed development of cirrhosis
    Jan Stindt
    Department of Gastroenterology, Hepatology and Infectiology, University Hospital, Dusseldorf, Germany Institute of Biochemistry, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Liver Int 33:1527-35. 2013
    ..Clinical phenotypes associated with BSEP mutations are commonly categorized as benign recurrent intrahepatic cholestasis (BRIC-2) or progressive familial intrahepatic cholestasis (PFIC-2)...
  17. doi Expression and localization of atypical PKC isoforms in liver parenchymal cells
    Claudia Stross
    Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University Dusseldorf, D 40225 Dusseldorf, Germany
    Biol Chem 390:235-44. 2009
    ..This topology suggests a specific function of aPKCs at the canalicular membrane in addition to their known role in cell polarity of epithelial cells...
  18. ncbi Inborn errors of biliary canalicular transport systems
    Ralf Kubitz
    Clinic for Gastroenterology, Hepatology and Infectiology, , Germany
    Methods Enzymol 400:558-69. 2005
    ..Only recently was it recognized that BRIC, which was estimated as a milder form of PFIC-1, may be caused by more than one gene...
  19. pmc Heterologous overexpression and mutagenesis of the human bile salt export pump (ABCB11) using DREAM (Directed REcombination-Assisted Mutagenesis)
    Jan Stindt
    Institute of Biochemistry, Heinrich Heine University, Dusseldorf, Germany
    PLoS ONE 6:e20562. 2011
    ..cerevisiae-compatible plasmid and analyzing the impact of a BSEP mutation in several mammalian cell lines...
  20. doi The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders
    Verena Keitel
    Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Dusseldorf, Germany
    Hepatology 50:861-70. 2009
    ..Conclusion: The data suggest a role for TGR5 in bile acid-induced fluid secretion in biliary epithelial cells...
  21. ncbi De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis
    Verena Keitel
    Department of Gastroenterology, Heinrich Heine University of Dusseldorf, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Hepatology 50:510-7. 2009
    ..The findings illustrate a novel disease mechanism due to a new class of functionally relevant autoantibodies resulting in cholestasis and subsequent liver failure...
  22. ncbi The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells
    Verena Keitel
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Dusseldorf, Germany
    Hepatology 45:695-704. 2007
    ..In addition, bile acids activated eNOS by phosphorylation of eNOS at amino acid position 1177. In line with eNOS activation, bile acids induced NO production in liver slices. This is the first report on the expression of TGR5 in SEC...
  23. ncbi Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis
    Anja Muhlfeld
    Clinic for Gastroenterology, Hepatology and Infectiology, Universitatsklinikum Dusseldorf, Moorenstrasse 5, Germany
    Arch Biochem Biophys 413:32-40. 2003
    ..The data show that oral supplementation of taurine induces Mrp2 and Bsep expression and may prevent LPS-induced cholestasis...
  24. pmc Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference
    Gerald Kircheis
    Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University Dusseldorf, Moorenstrasse 5, Dusseldorf 40225, Germany
    World J Gastroenterol 18:1077-84. 2012
    ..To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan© (FS)] as a reference...
  25. ncbi Osmoregulation of bile formation
    Ralf Kubitz
    Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Methods Enzymol 428:313-24. 2007
    ..Thus, osmoregulation of bile formation is of physiological and pathophysiological interest...
  26. ncbi Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion
    Marcus Schmitt
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Dusseldorf, Germany
    J Hepatol 41:274-83. 2004
    ..Vascular endothelial growth factor (VEGF) is expressed by many tumors, including hepatocellular carcinoma (HCC) and is involved in tumor angiogenesis. Little is known about its role for HCC infiltration into normal liver parenchyma...
  27. pmc Endocrine and paracrine role of bile acids
    Verena Keitel
    Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, Dusseldorf D 40225, Germany
    World J Gastroenterol 14:5620-9. 2008
    ..Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracellular kinases and of the plasma membrane-bound, G-protein coupled bile acid receptor TGR5/Gpbar-1...
  28. ncbi Molecular aspects of medicine: from experimental to clinical hepatology
    Dieter Haussinger
    Clinic for Gastroenterology, Hepatology and Infectiology, Medizinische Universitätsklinik Düsseldorf, Heinrich Heine University, Moorenstrasse 5, Dusseldorf 40225, Germany
    Mol Aspects Med 25:221-360. 2004
  29. doi Mycoplasma salivarium detected in a microbial community with Candida glabrata in the biofilm of an occluded biliary stent
    Birgit Henrich
    Institute of Medical Microbiology and Hospital Hygiene, Clinical Centre of Heinrich Heine University, Moorenstrasse 5, 40225 Duesseldorf, Germany
    J Med Microbiol 59:239-41. 2010
    ..We describe here, for what is believed to be the first time, the detection of M. salivarium, together with Candida glabrata, in an occluded biliary stent of an icteric, cholestatic patient...
  30. doi A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults
    Daniel Gotthardt
    Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
    Hepatology 48:1157-66. 2008
    ..2362C>T (p.Arg788Trp) which cosegregated with severity of disease. Bile from a mutation homozygote showed a reduced phosphatidylcholine/bile acid ratio, consistent with reduced ABCB4 phosphatidylcholine transport activity...