2006 Fiscal Year Final Research Report Summary
Molecular basis for hypoxic sensing and regulation of ventilatory responses
| Project/Area Number |
16390071
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIBAHARA Shigeki Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (70206142)
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| Co-Investigator(Kenkyū-buntansha) |
HIDA Wataru Tohoku University, Graduate School of Information Sciences, Professor, 大学院情報科学研究科, 教授 (10142944)
FURUYAMA Kazumichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (80280874)
TAKEDA Kazuhisa Tohoku University, Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (30311559)
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| Project Period (FY) |
2004 – 2006
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| Keywords | heme oxygenase / MITF / oxygen sensor / ventilatory response / erythrocyte |
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| Research Abstract |
We have shown that homozygous mice lacking heme oxygenase-2 (HO-2) show blunted hypoxic ventilatory response and homozygous black-eyed white (bw) mice, a mutant in microphthalmia-associated transcription factor (Mitf), show augmented hypoxic ventilatory response. These results suggest the involvement of HO-2 and Mitf in hypoxic ventilatory response. Moreover, we have obtained the following results.
1 HO-2 deficient mice exhibit mild hypxoemia and thickening of the pulmonary venous myocardium, in which HO-1,an inducible isozyme of heme oxygenase, is over-expressed.
2 The expression levels of HO-1 and HO-2 proteins were transiently decreased in the mouse liver at 7 days of normobaric hypoxia, whereas HO-1 and HO-2 proteins were increased in the heart at 28 days of hypoxia.
3 Using nine inbred mouse strains, we measured ventilatory responses to hypoxia (10% O_2) and hypercapnia (10% CO_2) of unanesthetized mice by whole body plethysmography. Basal respiratory variables and hypoxic ventilatory responses differed among the strains, but the hypercapnic ventilatory response did not differ. The hypoxic ventilatory response was the lowest in SWR/J mice. Thus, genetic factors may have influenced the hypoxic ventilatory response.
4 Using cDNA microarrays, we have identified lipocalin-type prostaglandin D synthase (L-PGDS), whose mRNA is undetectable in the homozygous bw mouse skin. L-PGDS represents a newly identified melanocyte marker. MITF may modulate the production of prostaglandin D_2 by activating the L-PGDS gene in melanocytes.
5 Hypoxia (1% O_2) reduces the expression levels of HO-1 and HO-2 protein in several human cell lines, such as YN-1 human erythroleukemia and HepG2 human hepatoma, after 48 h of incubation. Moreover, heme contents were increased in YN-1 and HepG2 cells after 48-h incubation under hypoxia.
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[Journal Article] Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activity.2006
Author(s)
Furuyama K, Harigae H, Heller T, Hamel BC, Minder EI, Shimizu T, Kuribara T, Blijlevens N, Shibahara S, Sassa S
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Journal Title
Eur.J.Haematol. 76 (1)
Pages: 33-41
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.2004
Author(s)
Adachi T, Ishikawa K, Hida W, Matsumoto H, Masuda T, Date F, Ogawa K, Takeda K, Furuyama K, Zhang Y, Kitamuro T, Ogawa H, Maruyama Y, Shibahara S
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Journal Title
Biochem.Biophys.Res.Commun. 320 (2)
Pages: 514-522
Description
「研究成果報告書概要(欧文)」より
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