Glucose is necessary for stabilization of hypoxia-inducible factor-1alpha 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-1alpha (HIF-1alpha) protein under hypoxic conditions. 6-Aminonicotinamide (6-AN), an inhibitor of the pentose phosphate pathway (PPP), also inhibited the increase of HIF-1alpha protein under hypoxic conditions, while the reduced protein levels of HIF-1alpha 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-1alpha protein. On the other hand, cobalt-induced expression of HIF-1alpha 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-1alpha protein under hypoxic conditions.
Osada-Oka
Mayuko
M
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan. osada@med.osaka-cu.ac.jp
Hashiba
Yasushi
Y
Akiba
Satoshi
S
Imaoka
Susumu
S
Sato
Takashi
T
D015120:6-Aminonicotinamide; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000235:genetics; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007976:Leupeptins; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D007976:Leupeptins; D034741:RNA, Small Interfering; D015120:6-Aminonicotinamide; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D005947:Glucose; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde