Inhibitory effect of 6-formylpterin on HIF-1alpha protein accumulation.
Hypoxia-inducible factor-1 (HIF-1) is a main regulator of metabolic adaptation to hypoxia. HIF-1alpha is induced by hypoxia, or by hypoxia-mimicking reagents, such as desferrioxamine (DFX), under a normoxic condition. A xanthine oxidase inhibitor, 6-formylpterin (6FP), is reported to exert its functions on reactive oxygen species (ROS) modulation. In this study, we investigated the effect of 6FP on HIF-1alpha expression under a DFX-treated or hypoxic condition. 6FP decreased HIF-1alpha expression at the protein level, but not at the mRNA level, in a dose-dependent manner, and this suppressive effect was reversed by the antioxidant, N-acetyl-L-cysteine (NAC). Furthermore, the ROS generated by 6FP was reversed with NAC coincubation. These findings suggest that intracellular ROS generated by 6FP decreased the HIF-1alpha protein accumulation under a DFX-treated or hypoxic condition.
Sommani
Piyanart
P
Institute of Advanced Energy, Kyoto University, Uji, Japan.
Yamashita
Kouhei
K
Miyoshi
Takashi
T
Tsunemine
Hiroko
H
Kodaki
Tsutomu
T
Mori
Hiroko
H
Hirota
Kiichi
K
Arai
Toshiyuki
T
Sasada
Masataka
M
Makino
Keisuke
K
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000473:pathology; D011622:Pterins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011622:Pterins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C005926:2-amino-4-hydroxy-6-formylpteridine; D003676:Deferoxamine; D000111:Acetylcysteine