期刊
JOURNAL OF ANESTHESIA
卷 24, 期 1, 页码 54-60出版社
SPRINGER JAPAN KK
DOI: 10.1007/s00540-009-0829-1
关键词
Propofol; Hypoxia-inducible factor 1; Macrophage; Glucose metabolism
资金
- Grants-in-Aid for Scientific Research [22791429, 22791428] Funding Source: KAKEN
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. 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-1 alpha and HIF-1 beta 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. Propofol suppressed HIF-1 alpha 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-1 alpha 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. 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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