Journal of Anesthesia

, Volume 24, Issue 1, pp 54–60 | Cite as

The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages

  • Tomoharu Tanaka
  • Satoshi Takabuchi
  • Kenichiro Nishi
  • Seiko Oda
  • Takuhiko Wakamatsu
  • Hiroki Daijo
  • Kazuhiko Fukuda
  • Kiichi Hirota
Original Article

Abstract

Purpose

Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor of hypoxia-induced gene expression. Anesthetics and perioperative drugs have been reported to affect HIF-1 activity. However, the effect of propofol on HIF-1 activity is not well documented. In this study, we investigated the effect of propofol on HIF-1 activation using macrophage-differentiated THP-1 cells.

Methods

Cells were exposed to lipopolysaccharide (LPS) under 20 or 1% O2 conditions with or without propofol treatment. The cell lysate was subjected to Western blot analysis using anti-HIF-1α and HIF-1β antibodies. HIF-1-dependent gene expression was investigated by quantitative real-time reverse-transcriptase PCR analysis and luciferase assay. The amount of cellular lactate and ATP was assayed.

Results

Propofol suppressed HIF-1α protein accumulation induced by LPS, but not by hypoxia in the THP-1 cells in a dose-dependent manner by inhibiting the neo-synthesis of HIF-1α protein. Induction of the HIF-1 downstream gene expression including glucose transporter 1, enolase 1, lactate dehydrogenase A, pyruvate dehydrogenase kinase-1 and vascular endothelial growth factor was inhibited by propofol. Propofol suppressed LPS-induced lactate accumulation and ATP content in THP-1 cells.

Conclusion

Our experimental results indicate that propofol inhibits HIF-1 activation and downstream gene expression induced by LPS and suppressed HIF-1-dependent glucose metabolic reprogramming. HIF-1 suppression by propofol in macrophages may explain molecular mechanisms behind the inhibitory effect of propofol on cellular inflammatory responses.

Keywords

Propofol Hypoxia-inducible factor 1 Macrophage Glucose metabolism 

Notes

Acknowledgment

We thank Dr. Gregg L. Semenza for providing plasmids.

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Copyright information

© Japanese Society of Anesthesiologists 2009

Authors and Affiliations

  • Tomoharu Tanaka
    • 1
  • Satoshi Takabuchi
    • 1
  • Kenichiro Nishi
    • 2
  • Seiko Oda
    • 1
  • Takuhiko Wakamatsu
    • 1
  • Hiroki Daijo
    • 1
  • Kazuhiko Fukuda
    • 1
  • Kiichi Hirota
    • 1
  1. 1.Department of AnesthesiaKyoto University HospitalKyotoJapan
  2. 2.Department of AnesthesiologyKansai Medical UniversityMoriguchiJapan

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