論文がアクセプトされました

On 2009/6/30 火曜日, in hypoxia reseacrh, by bodyhacker

W松先生の論文がacceptされました。

一安心

The intravenous anesthetics barbiturates inhibit hypoxia-inducible factor 1 activation

EUROPEAN JOURNAL OF PHARMACOLOGY

Abstract

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 barbiturates on HIF-1 activity has not been reported.  In this study, we investigated the effect of thiopental and thiamylal on HIF-1 activity using the neuronal SH-SY5Y cells, the non-neuronal HEK293 cells, and the macrophage-differentiated THP-1 cells.  Cells were exposed to 20% or 1% O2 conditions with or without thiopental or thiamylal treatment.  The cell lysate were subjected to Western blot analysis using anti-HIF-1α and -HIF-1β antibodies.

HIF-1-dependent gene expression was investigated by semi-quantitative real-time RT-PCR and luciferase assay.  Hydroxylation of HIF-1α protein was evaluated by in vitro pulldown assay using recombinant protein.  Both thiopental and thiamylal reversibly suppressed hypoxia-induced HIF-1 activation in the neuronal and the non-neuronal cells in a dose-dependent manner.  Moreover, the barbiturates inhibited lipopolysaccharide-induced HIF-1α expression in THP-1 cells.  The HIF-1-downstream gene expression was also inhibited by the barbiturates.  HIFα-hydroxylases activity and HIF-1α stability were not affected but the HIF-1α protein neo-synthesis was inhibited by the barbiturates.  Our experimental results indicate that barbiturates inhibit induced HIF-1 activation and downstream genes expression.

Keywords: anesthetic, barbiturate, hypoxia, hypoxia-inducible factor 1 (HIF-1), neuron, translation, macrophage


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