2010 Fiscal Year Final Research Report
The role of nardilysin in body temperature homeostasis
| Project/Area Number |
20200068
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
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| Allocation Type | Single-year Grants |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
Functional biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
HIRAOKA Yoshinori Kyoto University, 医学研究科, 助教 (60397552)
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| Co-Investigator(Renkei-kenkyūsha) |
NISHI Eiichiro 京都大学, 医学研究科, 准教授 (30362528)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 体温恒常性 / 適応熱産生 / 褐色脂肪組織 / メタロプロテアーゼ |
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| Research Abstract |
Nardilysin (N-arginine dibasic convertase ; NRDc) is a metalloendopeptidase of M16 family. We have generated NRDc knockout mice (NRDc-/-) by gene targeting. NRDc-/- mice showed cold-intolerance when exposed to cold temperature (4℃). Brown adipose tissue (BAT) is specialized for adaptive thermogenesis in response to cold exposure, which occurs through the activity of uncoupling protein 1 (UCP1). UCP1, a mitochondrial inner-membrane protein, uncouples the mitochondrial proton gradient from ATP production, which results in heat generation. We have evaluated the expression of thermogenic genes including UCP1 in BAT of wild-type (NRDc+/+) and NRDc-/- mice. Quantitative RT-PCR (qRT-PCR) analysis revealed that UCP1 mRNA expression level of NRDc-/- BAT did not change after cold exposure, while that of NRDc+/+ BAT was markedly increased. We have also evaluated changes in tail blood flow after cold exposure by using laser doppler flowmetry. While tail blood flow of NRDc+/+ mice was dramatically reduced after cold exposure, that of NRDc-/- mice was not affected. These results indicate that NRDc-/- mice could not keep their body temperature after cold exposure because of (i) impaired adaptive thermogenesis and (ii) impaired vasoconstriction.
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Author(s)
Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, Hosokawa, S Elbahrawy A, Soeda T, Koizumi M, Masui T, Kawaguchi M, Takaori K, Doi R, Nishi E, Kakinoki R, Deng JM, Behringer RR, Nakamura T, Uemoto S.
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Author(s)
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Author(s)
Hoshino K, Horiuchi H, Tada T, Tazaki J, Nishi E, Kawato M, Ikeda T, Yamamoto H, Akao M, Furukawa Y, Shizuta S, Toma M, Tamura T, Saito N, Doi T, Ozasa N, Jinnai T, Takahashi K, Watanabe H, Yoshikawa Y, Nishimoto N, Ouchi C, Morimoto T, Kita T, Kimura T.
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Journal Title
Circ J. 73
Pages: 336-342
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[Presentation] Clopidogrel Resistance inJapanese Patients Scheduled for Percutaneous Coronary Intervention, Poster Session2009
Author(s)
Tada T, Horiuchi H, Nagai K, Tazaki J, Nishi E, Touma M, Tamura T, Akao M, Furukawa Y, Kimura T, Kita T.
Organizer
The 73^rd Annual Scientific Meeting of the Japanese Circulation Society
Place of Presentation
Osaka
Year and Date
20090320-20090322
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