Klotho gene and endothelial function
The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifest...
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| Published in | Nihon Rōnen Igakkai zasshi Vol. 43; no. 3; pp. 342 - 344 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
Japan
The Japan Geriatrics Society
2006
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0300-9173 |
| DOI | 10.3143/geriatrics.43.342 |
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| Abstract | The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Systemic nitric oxide production was also significantly reduced in klotho deficient mice. Oxidative stress was increased in klotho deficient mice. The klotho gene delivery improves multiple aging phenotypes. Our findings establish the basis for the therapeutic potential of klotho gene delivery in age-related diseases. |
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| AbstractList | The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Systemic nitric oxide production was also significantly reduced in klotho deficient mice. Oxidative stress was increased in klotho deficient mice. The klotho gene delivery improves multiple aging phenotypes. Our findings establish the basis for the therapeutic potential of klotho gene delivery in age-related diseases.The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Systemic nitric oxide production was also significantly reduced in klotho deficient mice. Oxidative stress was increased in klotho deficient mice. The klotho gene delivery improves multiple aging phenotypes. Our findings establish the basis for the therapeutic potential of klotho gene delivery in age-related diseases. The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Systemic nitric oxide production was also significantly reduced in klotho deficient mice. Oxidative stress was increased in klotho deficient mice. The klotho gene delivery improves multiple aging phenotypes. Our findings establish the basis for the therapeutic potential of klotho gene delivery in age-related diseases. |
| Author | Nakamura, Tetsuya Kurabayashi, Masahiko Nagai, Ryozo Saito, Yuichiro |
| Author_xml | – sequence: 1 fullname: Nagai, Ryozo organization: Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine – sequence: 1 fullname: Nakamura, Tetsuya organization: Clinical Investigation and Research Unit, Gunma University Hospital – sequence: 1 fullname: Saito, Yuichiro organization: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine – sequence: 1 fullname: Kurabayashi, Masahiko organization: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine |
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| References | 1) Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al.: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997; 390: 45-51. 7) Nagai T, Yamada K, Kim HC, Kim YS, Noda Y, Imura A, et al.: Cognition impairment in the genetic model of aging klotho gene mutant mice a role of oxidative stress. FASEB J 2003; 17: 50-52. 4) Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, et al.: Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett 1998; 424: 6-10. 5) Saito Y, Yamagishi T, Nakamura T, Ohyama Y, Aizawa H, Suga T, et al.: Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun 1998; 248: 324-329. 6) Nakamura T, Saito Y, Ohyama Y, Masuda H, Sumino H, Kuro-o M, et al.: Production of nitric oxide, but not prostacyclin, is reduced in klotho mice. Jpn J Pharmacol 2002; 89: 149-156. 3) Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998; 242: 626-630. 8) Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, et al.: In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 2002; 39: 838-843. 2) Shiraki-Iida T, Iida A, Nabeshima Y, Anazawa H, Nishikawa S, Noda M, et al.: Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene. J Gene Med 2000; 2: 233-242. |
| References_xml | – reference: 3) Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998; 242: 626-630. – reference: 1) Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al.: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997; 390: 45-51. – reference: 4) Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, et al.: Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett 1998; 424: 6-10. – reference: 6) Nakamura T, Saito Y, Ohyama Y, Masuda H, Sumino H, Kuro-o M, et al.: Production of nitric oxide, but not prostacyclin, is reduced in klotho mice. Jpn J Pharmacol 2002; 89: 149-156. – reference: 5) Saito Y, Yamagishi T, Nakamura T, Ohyama Y, Aizawa H, Suga T, et al.: Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun 1998; 248: 324-329. – reference: 8) Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, et al.: In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 2002; 39: 838-843. – reference: 7) Nagai T, Yamada K, Kim HC, Kim YS, Noda Y, Imura A, et al.: Cognition impairment in the genetic model of aging klotho gene mutant mice a role of oxidative stress. FASEB J 2003; 17: 50-52. – reference: 2) Shiraki-Iida T, Iida A, Nabeshima Y, Anazawa H, Nishikawa S, Noda M, et al.: Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene. J Gene Med 2000; 2: 233-242. |
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| SubjectTerms | Aging Aging - genetics Animals Arteriosclerosis Endothelial function Endothelium, Vascular - physiology Glucuronidase - deficiency Glucuronidase - genetics Humans Mice Mice, Transgenic Nitric oxide Nitric Oxide - biosynthesis Oxidative Stress Phenotype |
| Title | Klotho gene and endothelial function |
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