BIOCHEMICAL AND MICROARRAY ANALYSES OF BUPIVACAINE-INDUCED APOPTOSIS

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概要

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• The mechanism by which apoptosis is induced by local anesthetic bupivacaine, a potent uncoupler of mitochondrial oxidative phosphorylation, was investigated. In promyelocytic leukemia cells HL-60, bupivacaine induced formation of apoptotic bodies and DNA fragmentation in a time- and dose-dependent manner similar to typical apoptosis inducers. Caspase-3, -8 and -9, which play a pivotal role in the initiation and execution of receptor- or mitochondria-mediated apoptosis, were all clearly activated by bupivacaine in good correlation with the degree of DNA fragmentation. However, bupivacaine did not induce either mitochondrial permeability transition (PT) or release of cytochrome c in experiments with isolated mitochondria. These results suggest that an indirect action of bupivacaine on mitochondria occurs and that other mechanisms may be involved in bupivacaine-induced apoptosis. To obtain additional information concerning the mechanism of action involved in bupivacaine-induced apoptosis, a microarray analysis of gene expression in bupivacaine-treated HL-60 cells was carried out. Several apoptosis-related genes were found to be transcriptionally regulated by bupivacaine using a high-density cDNA microarray. The expression levels of heat shock protein 70 (HSP70), c-jun and c-fos genes were remarkably up-regulated and those of c-myc and poly (ADP ribose) polymerase (PARP) were down-regulated in bupivacaine-treated cells. These results are of value in developing a better understanding of the molecular mechanism of bupivacaine-induced apoptosis leading to neuro- or myotoxicity.

• 日本トキシコロジー学会の論文
• 2003-05-31

著者

• SHINOHARA Yasuo

  Faculty of Pharmaceutical Sciences, The University of Tokushima

• BABA Yoshinobu

  Faculty of Pharmaceutical Sciences, The University of Tokushima

• Shinohara Y

  Institute For Genome Research University Of Tokushima:faculty Of Pharmaceutical Sciences University

• Shinohara Yasuo

  Institute For Genome Research University Of Tokushima

• Shinohara Yasuo

  Faculty Of Pharmaceutical Sciences The University Of Tokushima:institute For Genome Research The Uni

• Ichikawa Tomokazu

  Institute For Genome Research. University Of Tokushima:faculty Of Pharmaceutical Sciences University

• Ichikawa Tomokazu

  Faculty Of Pharmaceutical Sciences The University Of Tokushima

• Shinohara Yasuo

  Faculty Of Pharmaceutical Sciences University Of Tokushima

• Unami A

  Faculty Of Pharmaceutical Sciences The University Of Tokushima:toxicology Research Laboratories Fuji

• UNAMI Akira

  Faculty of Pharmaceutical Sciences, The University of Tokushima

• Baba Yoshinobu

  Faculty Of Pharmaceutical Sciences The University Of Tokushima:single Molecular Bioanalysis Laborato

• Shinohara Yasuo

  Faculty Of Pharmaceutical Sciences The University Of Tokushima

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