Authors: Matthias Kappler, Helge Taubert, Johannes Schubert, Dirk Vordermark and Alexander W. Eckert

Matthias Kappler

Corresponding author: matthias.kappler@medizin.uni-halle.de
Department of Oral and Maxillofacial Plastic Surgery; Martin Luther University Halle-Wittenberg; Halle, Germany

Helge Taubert

Department of Oral and Maxillofacial Plastic Surgery; Martin Luther University Halle-Wittenberg; Halle, Germany; Clinic of Urology; FA University Hospital Erlangen-Nürnberg and Nikolaus-Fiebiger-Center for Molecular Medicine; FA University Erlangen-Nürnberg; Erlangen, Germany

Johannes Schubert

Department of Oral and Maxillofacial Plastic Surgery; Martin Luther University Halle-Wittenberg; Halle, Germany

Dirk Vordermark

Department of Radiotherapy; Martin-Luther-University Halle-Wittenberg; Halle, Germany
These authors contributed equally to this work

Alexander W. Eckert

Department of Oral and Maxillofacial Plastic Surgery; Martin Luther University Halle-Wittenberg; Halle, Germany
These authors contributed equally to this work

Abstract:
It is well known that the hypoxia-inducible factor 1 α (HIF1α) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1α is detectable even under normoxic conditions, if the metabolism is altered, e.g., high proliferation index. Importantly, both hypoxic metabolism and the Warburg effect have in common a decrease of the intracellular pH value.

In our interpretation, HIF1α is not directly accumulated by hypoxia, but by a process which occurs always under hypoxic conditions, a decrease of the intracellular pH value because of metabolic imbalances. We assume that HIF1α is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1α has its major role in activating genes to eliminate toxic metabolic waste products (e.g., NH₃/NH₄+) generated by the tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or the Warburg effect. For that reason, HIF1α appears as a potential target for tumor therapy to disturb the pH balance and to inhibit the elimination of toxic metabolic waste products in the tumor cells.

Received: July 23, 2012; Accepted: August 15, 2012; Published Online: September 17, 2012

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