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Z Gastroenterol 2006; 44(1): 67-76
DOI: 10.1055/s-2005-858987
Übersicht

© Karl Demeter Verlag im Georg Thieme Verlag KG Stuttgart · New York

Oxygen: Modulator of Physiological and Pathophysiological Processes in the Liver

Sauerstoff: Modulator von physiologischen und pathophysiologischen Prozessen in der LeberT. Kietzmann1 , E. Y. Dimova1 , D. Flügel1 , J.-G Scharf2
  • 1Department of Biochemistry, Faculty of Chemistry, University of Kaiserslautern
  • 2Medizinische Klinik und Poliklinik, Georg-August-Universität, Göttingen
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Publication History

Publication Date:
05 January 2006 (online)

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Zusammenfassung

Molekularer Sauerstoff hat bedeutende Funktionen als Substrat bei einer Reihe biochemischer Reaktionen und als Signalmolekül bei der Modulation der Genexpression. Dies ist besonders markant in der Leber, wo der physiologisch vorhandene Sauerstoffgradient bedeutend für die metabolischen Zonierung ist. Neben der Sauerstoffsignalkette sind auch die Nährstoff (Glukose)-abhängigen Signalwege für die Zonierung bedeutend und so können Wechselwirkungen zwischen Sauerstoffsignalweg und Glukosesignalweg mit für die dynamische Zonierung in der Leber verantwortlich sein. Unter pathologischen Bedingungen kann eine Unterversorgung des Lebergewebes mit Sauerstoff (Hypoxie) ein entscheidender Faktor für die Progression von Lebererkrankungen und insbesondere Krebs sein. Dabei spielen die Transkriptionsfaktoren der HIF-Familie eine bedeutende Rolle; deren Wirkung kann partiell durch USF-Proteine antagonisiert werden. Weiterhin scheinen positive Rückkopplungsmechanismen zwischen Hypoxie, HIF und der IGF-Achse zu existieren, die die Wirkung von Hypoxie oder Wachstumsfaktoren verstärken können. Somit kann die genaue Kenntnis der einzelnen Signalwege und ihrer Wechselwirkungen eventuell dazu beitragen neue Therapiestrategien für Erkrankungen zu entwickeln, die durch eine veränderte Sauerstoffverfügbarkeit gekennzeichnet sind.

Abstract

Oxygen has important functions as substrate for biochemical reactions and as modulator of gene expression. In the liver, the physiologically occurring oxygen gradient is a major effector of metabolic zonation. In addition, cross-talks between the O2 signaling and nutrient signaling chains initiate a dynamic zonation pattern. Under pathological situations, hypoxia appears to be a major determinant for liver diseases and cancer. Thereby transcription factors of the HIF family are activated whereas USF proteins have the potential to counteract HIFs. In addition, feedback mechanisms between hypoxia, HIF and the IGF axes appear to exist. Thus, the knowledge of these mechanisms may help to initiate new therapies in diseases with disturbed O2 availability.

Schlüsselwörter

Metabolische Zonierung - IGF Bindungsprotein - Hypoxie - HIF - Tumor

Key words

Metabolic zonation - IGF binding protein-1 - HIF - PHD

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Dr. Thomas Kietzmann

Department of Biochemistry, Faculty of Chemistry, University of Kaiserslautern

67663 Kaiserslautern

Phone: ++ 49/6 31/2 05 49 53

Fax: ++ 49/6 31/2 05 34 19

Email: tkietzm@gwdg.de

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