Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany.
Cell Cycle. 2012 Nov 1;11(21):3932-6. doi: 10.4161/cc.21854. Epub 2012 Sep 17.
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.
众所周知，缺氧诱导因子 1α（HIF1α）可作为对缺氧的适应性代谢反应被检测到。然而，如果代谢发生改变，例如高增殖指数，即使在常氧条件下也可检测到 HIF1/HIF1α。重要的是，缺氧代谢和瓦博格效应都有一个共同点，即细胞内 pH 值下降。在我们的解释中，HIF1α不是直接由缺氧积累的，而是由一个总是在缺氧条件下发生的过程积累的，即由于代谢失衡导致细胞内 pH 值下降。我们假设 HIF1α是细胞内 pH 值的敏感控制器，与氧浓度无关。此外，HIF1α在激活基因以消除由肿瘤特异性代谢（称为谷氨酰胺分解）产生的有毒代谢废物（例如 NH3/NH4+）方面发挥主要作用，这些废物发生在缺氧或瓦博格效应期间。因此，HIF1α似乎是肿瘤治疗的一个潜在靶点，可以扰乱 pH 平衡并抑制肿瘤细胞中有毒代谢废物的消除。
