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2005年01月28日

The effects of local anesthetics on cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 1

The effects of local anesthetics on cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 1, Journal of Anesthesia
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Purpose  Hypoxia (reduced oxygen availability) induces a series of adaptive physiological responses. At the cellular level, the adaptation includes a switch of energy metabolism from oxidative phosphorylation to anaerobic glycolysis, increased glucose uptake, and the expression of stress proteins related to cell survival. One of the most important transcription factors that activate the expression of oxygen-regulated genes is hypoxia-inducible factor 1 (HIF-1). We previously reported that halothane inhibits the hypoxia-induced HIF-1 activation. In this study, we investigated the effect of local anesthetics on HIF-1 activation and its downstream gene expression.
Methods  The established cell line Hep3B and SK-N-MC cells were exposed to 1% O2 with or without treatment by either lidocaine or bupivacaine. Expression of subunits of HIF-1, HIF-1, and HIF-1 was examined by Western blot using specific antibodies. Expression of mRNA of HIF-1 and the HIF-1-dependent genes was investigated by RT-PCR and reporter assay.
Results  Neither of the local anesthetics tested affected the accumulation of HIF-1 induced by hypoxia, nor did they affect NOC18-induced HIF-1 accumulation. Moreover, they had no effects on HIF-1-mediated hypoxia-induced gene expression.
Conclusion  The local anesthetics lidocaine and bupivacaine did not affect the HIF-1-dependent cellular hypoxia-induced gene responses.

Key words  Local anesthetics - Hypoxia responses - Hypoxia-inducible factor 1

投稿者 hif1 : 2005年01月28日 09:13

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