The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages
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% $ O_{2} $ 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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Journal of anesthesia - 24(2009), 1 vom: 29. Dez., Seite 54-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tanaka, Tomoharu [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Glucose metabolism |
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| Anmerkungen: |
© Japanese Society of Anesthesiologists 2009 |
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| doi: |
10.1007/s00540-009-0829-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2036247946 |
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| 100 | 1 | |a Tanaka, Tomoharu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages |
| 264 | 1 | |c 2009 | |
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| 520 | |a 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% $ O_{2} $ 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. | ||
| 650 | 4 | |a Propofol | |
| 650 | 4 | |a Hypoxia-inducible factor 1 | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Glucose metabolism | |
| 700 | 1 | |a Takabuchi, Satoshi |4 aut | |
| 700 | 1 | |a Nishi, Kenichiro |4 aut | |
| 700 | 1 | |a Oda, Seiko |4 aut | |
| 700 | 1 | |a Wakamatsu, Takuhiko |4 aut | |
| 700 | 1 | |a Daijo, Hiroki |4 aut | |
| 700 | 1 | |a Fukuda, Kazuhiko |4 aut | |
| 700 | 1 | |a Hirota, Kiichi |4 aut | |
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