2006 Fiscal Year Final Research Report Summary
Analysis and Clinical Application of Gene Expression Changes Induced by Perioperative Stresses
| Project/Area Number |
16209046
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
FUKUDA Kazuhiko Kyoto University, Medicine, Professor, 医学研究科, 教授 (90199224)
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| Co-Investigator(Kenkyū-buntansha) |
SHODA Takehiro Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (60335263)
TSUJIKAWA Hiroshi Kyoto University, Medicine, Assistant Professor, 医学研究科, 助手 (20362501)
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| Project Period (FY) |
2004 – 2006
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| Keywords | stress response / proopiomelanocortin / serotonin / hypoxia / lymphocyte / anesthetics / nociceptin / gene expression |
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| Research Abstract |
This research was aimed to clarify cellular stress responses at molecular levels, to analyze modification of stress responses by perioperatively used drugs, and identify gene expression changes induced by perioperatively used drugs. The results obtained are summarized below.
1.Increase in plasma norepinephrine concentration induced by laparotomy in rats was suppressed by CRF-1 receptor antagonists. It was suggested that a pathway exists in the central nervous system which inhibits sympathetic nervous responses induced by surgical insults.
2.Effects of perioperatively used drugs on the proopiomelanocortin (POMC) gene expression was analyzed by a pituitary tumor cell line (AtT20PL) which was stably transfected with the POMC gene promoter linked with the luciferase gene. It was shown that calcium channel blockers and local anesthetics can potentiate CRH-induced POMC gene expression.
3.Isoflurane, a prototype of volatile anesthetics, suppresses serotonin release in the cerebral cortex, which can be related with sedative action of isoflurane. On the other hand, nitrous oxide was shown to increase serotonin release in the spinal cord, which was suggested to be involved in the antinociceptive action of nitrous oxide at the spinal cord level. Furthermore, analysis of nociceptin receptor knockout mice suggested that the nociceptin receptor is not involved in the anesthetic action of volatile anesthetics but contributes to the antinociceptive action of nitrous oxide.
4.Effects of various drugs on the hypoxia-induced gene expression changes mediated by hypoxia-inducible factor (HIF- 1). It was shown that a vasodilator sodium nitroprusside and a n intravenous anesthetic agent propofol inhibit hypoxia-induced HIF-1 activation.
5.Morphine-induced gene expression changes in T-lymphocytes were identified. It was shown that expression of apoptosis-related genes was increased by morphine.
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[Journal Article] Activation of hypoxia-inducible factor 1 during macrophage differentiation.2006
Author(s)
Oda, T., Hirota, K., Nishi, K., Takabuchi, S., Oda, S., Yamada, H., Arai, T, Fukuda.K., Kita, T., Adachi, T., Semenza, G.L., Nohara, R.
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Journal Title
Am. J. Physiol. Cell Physiol. 291
Pages: C104-C113
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Omission of fentanyl during sevoflurane anesthesia decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in major breast cancer surgery.2006
Author(s)
Shirakami, G., Teratani, Y., Segawa, H., Matsuura, S., Shichino, T., Fukuda.K.
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Journal Title
J. Anesth. 20
Pages: 188-195
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition of E-selectin-mediated leukocyte adhesion by volatile anesthetics in a static condition.2005
Author(s)
Hisano, T., Namba, T., Hashiguchi-Ikeda, M., Itoh, T., Hirota, K., Fukuda, K.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The effect of local anesthetics on the cellular hypoxia- induced gene responses mediated by hypoxia-inducible factor 1.2005
Author(s)
Nishi, K., Hirota, K., Takabuchi, S., Oda, S., Fukuda, K., Adachi, T., Shingu, T.
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Journal Title
J Anesth. 19
Pages: 54-59
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nociceptin system does not affect MAC of volatile anaesthetics.2005
Author(s)
Himukashi, S., Miyazaki, Y., Koyanagi, S., Mukaida, K., Shichino, T., Uga, H., Fukuda, K.
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Journal Title
Acta Anaesthesiol. Scand. 49
Pages: 771-773
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protective effects of intracellular reactive oxygen species generated by 6-formylpterin on tumor necrosis factor-a-induced apoptotic cell injury in cultured rat hetatocytes.2005
Author(s)
Ishii, H., Arai, T., Mori, H., Yamada, H., Endo, N., Makino, K., Fukuda, K.
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Journal Title
Life Sci. 77
Pages: 858-868
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Delayed descharge and acceptability of ambulatory surgery in adult outpatients receiving general anesthesia.2005
Author(s)
Shirakami, G., Teratani, Y., Namba, T., Hirakata, H., Tazuke- Nishimura, M., Fukuda, K.
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Journal Title
J. Anesth. 19
Pages: 93-101
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo.2005
Author(s)
Tanimoto, K., Saito, Y., Hamanaka, I., Kuwahara, K., Harada, M., Takahashi, N., Kawakami, R., Nakagawa, Y., Nakanishi, M., Adachi, Y., Shirakami, G., Fukuda, K., Yoshimura, A., Nakao, K.
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Journal Title
Circ. J. 69
Pages: 1412-1417
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Opioid receptor stimulation does not affect cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 1 in cultured cell lines.2005
Author(s)
Takabuchi, S., Hirota, K,.Oda, S., Nish, K., Oda, T., Shingu, K., Adachi, T., Fukuda K.
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Journal Title
J. Anesth. 19(3)
Pages: 263-265
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling.2004
Author(s)
Kasuno, K., Takabuchi, S., Fukuda.K., Kizaka-Kondoh, S, Yodoi, J., Adachi, T., Semenza, G.L., Hirota, K.
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Journal Title
J. Biol. Chem. 279
Pages: 2550-2558
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner.2004
Author(s)
Takabuchi, S., Hirota, K., Nishi, K., Oda, S., Oda, T., Shingu, T., Takabayashi, A., Adachi, T., Semenza, G.L., Fukuda.K.
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Journal Title
FEBS Lett. 577
Pages: 434-438
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway.2004
Author(s)
Takabuchi, S., Hirota, K., Nishi, K., Oda, S., Oda, T., Shingu, T., Takabayashi, A., Adachi, T., Semenza, G.L., Fukuda.K.
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Journal Title
Biochem. Biophys. Res. Commun. 324
Pages: 417-423
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling.2004
Author(s)
Hirota, K., Fukuda, R., Takabuchi, S., Kizaka-Kondoh, S., Adachi, T., Fukuda.K., Semenza, G.L.
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Journal Title
J. Biol. Chem. 279
Pages: 41521-41528
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of intracellular reactive oxygen species generated by 6-formylpterin on T cell functions.2004
Author(s)
Arai, T., Yamada, H., Namba, T., Mori, H., Ishii, H., Yamashita, K., Sasada, M., Makino, K., Fukuda, K.
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Journal Title
Biochem. Pharmacol. 67
Pages: 1185-1193
Description
「研究成果報告書概要(欧文)」より
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