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

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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.

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Acknowledgment

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

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Authors and Affiliations

  1. Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-Ku, Kyoto, 6060-8507, Japan

    Tomoharu Tanaka, Satoshi Takabuchi, Seiko Oda, Takuhiko Wakamatsu, Hiroki Daijo, Kazuhiko Fukuda & Kiichi Hirota

  2. Department of Anesthesiology, Kansai Medical University, Moriguchi, Osaka, Japan

    Kenichiro Nishi

Authors
  1. Tomoharu Tanaka
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  2. Satoshi Takabuchi
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  3. Kenichiro Nishi
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  5. Takuhiko Wakamatsu
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  7. Kazuhiko Fukuda
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  8. Kiichi Hirota
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Corresponding author

Correspondence to Kiichi Hirota.

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Tanaka, T., Takabuchi, S., Nishi, K. et al. The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages. J Anesth 24, 54–60 (2010). https://doi.org/10.1007/s00540-009-0829-1

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  • DOI: https://doi.org/10.1007/s00540-009-0829-1

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