北野病院時代に外科と共同研究をしていた研究をまとめた論文がOKになりました。
木村先生おめでとう!!
n-propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems
Motohide Kimura, Satoshi Takabuchi, Tomoharu Tanaka, Miyahiko Murata, Kenichiro Nishi , Seiko Oda, Tomoyuki Oda, Michiyuki Kanai, Kazuhiko Fukuda, Shinae Kizaka-Kondo, Takehiko Adachi , Arimichi Takabayashi , Gregg L. Semenza , and Kiichi Hirota
Biochemical J. i in press
Abstract
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive responses to hypoxia. The expression and transcriptional activity of the HIF-1 subunit are stringently controlled by intracellular oxygen (O2) tension through the action of prolyl and asparaginyl hydroxylases. In this study we demonstrate that n-prolyl gallate (PG) 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-1a are increased by PG. PG treatment inhibits the interaction between HIF-1a and VHL and promotes the interaction between HIF-1 a and p300, indicating that PG inhibits the activity of both prolyl and asparaginyl HIF-1a hydroxylases. We conclude that PG activates HIF-1 and enhances the resultant gene expression by directly affecting the intracellular O2 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.
Keywords: HIF-1 hydroxylase, erythropoietin, VEGF, intestinal trefoil factor