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-Kondoh; Takehiko Adachi; Arimichi Takabayashi; Gregg L. Semenza; Kiichi Hirota

doi:10.1042/BJ20070824

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-Kondoh, Takehiko Adachi, Arimichi Takabayashi, Gregg L. Semenza, Kiichi Hirota

School of Medicine

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	97-105
Number of pages	9
Journal	Biochemical Journal
Volume	411
Issue number	1
DOIs	https://doi.org/10.1042/BJ20070824
State	Published - Apr 1 2008

Keywords

Erythropoietin
Hypoxia-inducible factor 1α (HIF-1α) hydroxylase
Intestinal trefoil factor
Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1042/BJ20070824

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title = "n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems",

abstract = "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.",

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author = "Motohide Kimura and Satoshi Takabuchi and Tomoharu Tanaka and Miyahiko Murata and Kenichiro Nishi and Seiko Oda and Tomoyuki Oda and Michiyuki Kanai and Kazuhiko Fukuda and Shinae Kizaka-Kondoh and Takehiko Adachi and Arimichi Takabayashi and Semenza, {Gregg L.} and Kiichi Hirota",

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T1 - n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems

AU - Kimura, Motohide

AU - Takabuchi, Satoshi

AU - Tanaka, Tomoharu

AU - Murata, Miyahiko

AU - Nishi, Kenichiro

AU - Oda, Seiko

AU - Oda, Tomoyuki

AU - Kanai, Michiyuki

AU - Fukuda, Kazuhiko

AU - Kizaka-Kondoh, Shinae

AU - Adachi, Takehiko

AU - Takabayashi, Arimichi

AU - Semenza, Gregg L.

AU - Hirota, Kiichi

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Y1 - 2008/4/1

N2 - 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.

AB - 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.

KW - Erythropoietin

KW - Hypoxia-inducible factor 1α (HIF-1α) hydroxylase

KW - Intestinal trefoil factor

KW - Vascular endothelial growth factor (VEGF)

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n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems

Abstract

Keywords

ASJC Scopus subject areas

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