The real face of HIF1α in the tumor process
Volume 11, Issue 21
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November 1, 2012
Pages 3932 - 3936http://dx.doi.org/10.4161/cc.21854
: HIF1α, Warburg effect, ammonium, glutaminolysis, hypoxia, metabolism, normoxia, tumor
Authors: Matthias Kappler, Helge Taubert, Johannes Schubert, Dirk Vordermark and Alexander W. Eckert View affiliations
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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