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

• Published in: Journal of anesthesia Vol. 19; no. 1; pp. 54 - 59
• Main Authors: Nishi, Kenichiro, Hirota, Kiichi, Takabuchi, Satoshi, Oda, Seiko, Fukuda, Kazuhiko, Adachi, Takehiko, Shingu, Koh
• Format: Journal Article
• Language: English
• Published: Japan Springer 01.02.2005
• Subjects: Anesthetics; Anesthetics, Local - pharmacology; Care and treatment; Cell Hypoxia - physiology; Cell Line, Tumor; Cells, Cultured; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Dosage and administration; Free Radical Scavengers - pharmacology; Genes, Reporter; Genetic aspects; Halothane - pharmacology; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; Nitric Oxide - pharmacology; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - physiology; Japan
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-004-0271-3

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. 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-1alpha, and HIF-1beta 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. Neither of the local anesthetics tested affected the accumulation of HIF-1alpha induced by hypoxia, nor did they affect NOC18-induced HIF-1alpha accumulation. Moreover, they had no effects on HIF-1-mediated hypoxia-induced gene expression. The local anesthetics lidocaine and bupivacaine did not affect the HIF-1-dependent cellular hypoxia-induced gene responses.