1998 Fiscal Year Final Research Report Summary
Physiological function of ageing suppression gene klotho and its role in development of adult disease
| Project/Area Number |
09470159
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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 |
Circulatory organs internal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
NAGAI Ryozo Gunma University School of Medicine, 2nd Dept of Int Med, Professor, 医学部, 教授 (60207975)
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| Co-Investigator(Kenkyū-buntansha) |
UTSUGI Toshihiro Gunma University School of Medicine, 2nd Dept of Int Med, Assistant, 医学部, 教務員 (10282386)
ARAI Masashi Gunma University School of Medicine, 2nd Dept of Int Med, Assistant, 医学部, 助手 (60270857)
NAKAMURA Tetsuya Gunma University School of Medicine, 2nd Dept of Int Med, Assistant Professor, 医学部, 講師 (10272238)
KURABAYASHI Masahiko Gunma University School of Medicine, 2nd Dept of Int Med, Associate Professor, 医学部, 助教授 (00215047)
NABESHIMA Yo-ichi Kyoto University, Faculties & Graduated School of Medicine, Dept of Pathology, P, 大学院・研究科, 教授 (60108024)
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| Project Period (FY) |
1997 – 1998
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| Keywords | AGING / ENDOTHELIUM / NITRIC OXIDE / PARABIOSIS / HUMORAL FACTOR / HYPERTENSION / KLOTHO |
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| Research Abstract |
Arteriosclerosis caused by aging is recognized to be a crucial risk factor of cardiovascular disease. We recently established Klotho mouse which causes age-related disorders including arteriosclerosis. However, no information on endothelial function of Klotho mouse or the pathophysiological role of klotho gene product as a circulating factor is available. We demonstrate that the vasodilator response of aorta and arterioles to acetylcholine was significantly attenuated in homozygous klotho mice as compared with wild-type mice. Parabiosis between wild-type and heterozygous klotho mice resulted in restoration of endothelial function in heterozygous Klotho mice. Nitric oxide metabolites (NO2- and NO3-) in urine are significantly lower in heterozygous Klotho mice (142 *16nmol/day) than wild-type mice (241* 28nmol/day). We also showed that kiotho mRNA expression is significantly decreased in spontaneously hypertensive rats, deoxycorticosterone acetate (DOCA) salt hypertensive rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats developing hypertension, obesity, insulin resistance, and hypertriglyceridemia.
We conclude that the Klotho protein protects against the cardiovascular dysfunction through endothelium-derived NO production by humoral pathways.
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[Publications] Kuro-o M,Matsumura Y,Aizawa H,Kawaguchi h, Suga T,Utsugi T,Ohyama Y,Kurabayashi M,Kaname T,Kume E,Iwasaki H,Iida A,Shiraki-Iida T,Nishikawa S,Nagai R, Nabeshima Y.: "Mutation of the mouse Klotho gene leads to a syndrome resembling ageing." Nature.390(6655). 45-51 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Saito Y,Yamagishi T,Nakamura T,Ohyama Y,Aizawa H,Suga T,Matsumura Y,Masuda H,Kurabayashi M,Kuro-o M,Nabeshima Y,Nagai R.: "Klotho protein protects ageinst endothelial dysfunction." Biochem Biophys Res Commun. 248(2). 324-329 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Aizawa H,Saito Y,Nakamura T,Inoue M,Imanari T,Ohyama Y,Matsumura Y,Masuda H,Oba S,Mise N,Kimura K,Hasegawa A,Kurabayashi M,Kuro-o M,Nabeshima Y,Nagai R.: "Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats." Biochem Biophys Res Commun. 249(3). 865-871 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohyama Y,Kurabayashi M,Masuda H,Nakamura T,Aihara Y,Kaname T,Suga T,Arai M,Aizawa H,Matsumura Y,Kuro-o M,Nabeshima Y,Nagai R: "Molecular cloning of rat klotho cDNA : markedly decreased expression of klotho by acute inflammatory stress." Biochem Biophys Res Comm. 251(3). 920-925 (1998)
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「研究成果報告書概要(欧文)」より
