HIF-1 (hypoxia-inducible factor 1) is a master regulator of cellular adaptive responses to hypoxia. The expression and transcriptional activity of the HIF-1α subunit is stringently controlled by intracellular oxygen tension through the action of prolyl and asparaginyl hydroxylases. In the present study we demonstrate that PG (n-propyl gallate) activates HIF-1 and expression of its downstream target genes under normoxic conditions in cultured cells and in mice. The stability and transcriptional activity of HIF-1α are increased by PG. PG treatment inhibits the interaction between HIF-1α and VHL (von Hippel–Lindau protein) and promotes the interaction between HIF-1α and p300, indicating that PG inhibits the activity of both prolyl and asparaginyl HIF-1α hydroxylases. We conclude that PG activates HIF-1 and enhances the resultant gene expression by directly affecting the intracellular oxygen sensing system in vitro and in vivo and that PG represents a lead compound for the development of a non-toxic activator of HIF-1.
n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems
- Views Icon Views
- Share Icon Share
- Cite Icon Cite
Motohide Kimura, Satoshi Takabuchi, Tomoharu Tanaka, Miyahiko Murata, Kenichiro Nishi, Seiko Oda, Tomoyuki Oda, Michiyuki Kanai, Kazuhiko Fukuda, Shinae Kizaka-Kondoh, Takehiko Adachi, Arimichi Takabayashi, Gregg L. Semenza, Kiichi Hirota; n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems. Biochem J 1 April 2008; 411 (1): 97–105. doi: https://doi.org/10.1042/BJ20070824
Download citation file: