Startseite HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion

  • Markus G. Donner EMAIL logo , Stefan A. Topp , Patricia Cebula , Anna Krienen , Thor Gehrmann , Annika Sommerfeld , Roland Reinehr , Arne Macher , Diran Herebian , Ertan Mayatepek , Benedikt H. Pannen , Wolfram T. Knoefel und Dieter Häussinger
Veröffentlicht/Copyright: 4. Dezember 2012
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 394 Heft 1

Abstract

We studied the downregulation of hepatobiliary transport systems and the effect of pharmacological heme oxygenase-1 (HO-1) preinduction by Hemoglobin-Glutamer 200 (HbG200) in cold ischemia-reperfused rat liver (I/R). Cold I/R reduced bile flow in the reperfusion period from 3.10±0.10 ml/3 h to 0.54±0.20 ml/3 h (p<0.05) and biliary taurocholate excretion from 45.9±13.81 μmol/3 h to 1.87±0.46 μmol/3 h (p<0.05). Mrp2, Bsep and Ntcp peak immunofluorescence in pericentral hepatocytes decreased to 79.0±2.6% (p<0.001), 80.6±8.4% (p<0.05) and 65.8±5.0% (p<0.01), respectively. Pre-induction of HO-1 by HbG200 was largely confined to pericentral hepatocytes. HO-1 induction attenuated the decreased bile flow (0.91±0.16 ml/3 h, p<0.05) and canalicular taurocholate secretion (4.33±1.71 μmol/3 h, p<0.05). Bsep and Mrp2 peak immunofluorescence in pericentral hepatocytes was largely restored. Activation of JNK and Fyn by cold I/R was significantly attenuated by HO-1. Inhibiting HO activity by tin protoporphyrin IX after HbG200 administration reversed the effect on bile flow and canalicular transporter expression. In conclusion, pericentral downregulation of Bsep and Mrp2 following cold I/R is ameliorated by inducing HO-1 and was associated with diminished hepatocellular JNK and Fyn signaling. HO-1 may serve as a therapeutic target to attenuate hepatocellular cholestasis following I/R injury.

Keywords: cholestasis; hepatobiliary transport; ischemia reperfusion injury
Corresponding author: Markus G. Donner, Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University Düsseldorf, D-40225 Düsseldorf, Germany
Received: 2012-3-14
Accepted: 2012-8-2
Published Online: 2012-12-04
Published in Print: 2013-01-01

©2012 by Walter de Gruyter Berlin Boston

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Reviews
  4. Exosomes: the ideal nanovectors for biodelivery
  5. Biological applications of the electrochemical sensing of nitric oxide: fundamentals and recent developments
  6. Minireview
  7. Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling
  8. Research Articles/Short Communications
  9. Protein Structure and Function
  10. Diversity, abundance, and sex-specific expression of chemosensory proteins in the reproductive organs of the locust Locusta migratoria manilensis
  11. Structure of the Ca2+-saturated C-terminal domain of scallop troponin C in complex with a troponin I fragment
  12. An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2
  13. Reengineering of subtilisin Carlsberg for oxidative resistance
  14. New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm
  15. Cell Biology and Signaling
  16. HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion
  17. Effect of silver nanoparticles on human primary keratinocytes
  18. Multifunctional silica nanoparticles for optical and magnetic resonance imaging
  19. Proteolysis
  20. Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases
https://doi.org/10.1515/hsz-2012-0153
Schlagwörter für diesen Artikel
cholestasis; hepatobiliary transport; ischemia reperfusion injury

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Reviews
  4. Exosomes: the ideal nanovectors for biodelivery
  5. Biological applications of the electrochemical sensing of nitric oxide: fundamentals and recent developments
  6. Minireview
  7. Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling
  8. Research Articles/Short Communications
  9. Protein Structure and Function
  10. Diversity, abundance, and sex-specific expression of chemosensory proteins in the reproductive organs of the locust Locusta migratoria manilensis
  11. Structure of the Ca2+-saturated C-terminal domain of scallop troponin C in complex with a troponin I fragment
  12. An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2
  13. Reengineering of subtilisin Carlsberg for oxidative resistance
  14. New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm
  15. Cell Biology and Signaling
  16. HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion
  17. Effect of silver nanoparticles on human primary keratinocytes
  18. Multifunctional silica nanoparticles for optical and magnetic resonance imaging
  19. Proteolysis
  20. Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 21.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2012-0153/html
Button zum nach oben scrollen