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Glucose is necessary for stabilization of hypoxia‐inducible factor‐1α under hypoxia: Contribution of the pentose phosphate pathway to this stabilization
Author(s) -
Osada-Oka Mayuko,
Hashiba Yasushi,
Akiba Satoshi,
Imaoka Susumu,
Sato Takashi
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.05.046
Subject(s) - pentose phosphate pathway , glycolysis , hypoxia (environmental) , chemistry , dehydrogenase , biochemistry , glucose 6 phosphate dehydrogenase , hypoxia inducible factors , carbohydrate metabolism , fructose , pentose , metabolism , enzyme , medicine , oxygen , gene , organic chemistry , fermentation
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.