Glucose is necessary for stabilization of hypoxia-inducible factor-1α under hypoxia: Contribution of the pentose phosphate pathway to this stabilization

In this study, we observed that low glucose or fructose reduces the increase in hypoxia-inducible factor-1α (HIF-1α) protein under hypoxic conditions. 6-Aminonicotinamide (6-AN), an inhibitor of the pentose phosphate pathway (PPP), also inhibited the increase of HIF-1α protein under hypoxic conditions, while the reduced protein levels of HIF-1α by low glucose were apparently recovered by the addition of MG-132 or NADPH. Moreover, siRNA for glucose-6-phosphate dehydrogenase, which produces NADPH, reduced the increase in HIF-1α protein. On the other hand, cobalt-induced expression of HIF-1α protein was not affected by low glucose or 6-AN under normoxic conditions. In conclusion, glucose metabolism through the PPP, but not in glycolysis, plays an important role in the stabilization of HIF-1α protein under hypoxic conditions.