2007 Fiscal Year Final Research Report Summary
Studies on novel peptide hormones in the pathophy siology of obesity and hypertension
| Project/Area Number |
18590282
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
TAKAHASHI Kazuhiro Tohoku University, Tohoku University, School of Medicine, Professor (80241628)
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| Co-Investigator(Kenkyū-buntansha) |
TOTSUNE Kazuhito Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor (10217515)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Adrenomedullin / Hypertension / Transcription / Adipocyte / Adipokine / Oxidative stress / Kidnev / Metabolic syndrome |
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| Research Abstract |
Adrenomedullin is a multifunctional peptide with vasodilator activity, anti-oxidative stress action, etc.
Takahashi ed. al. have shown for the first time that adrenomedullin is expressed in adipocytes and one of the adipokines. Adipocytes have two mechanisms for up-regulation and down-regulation of the adrenomedullin expression. We have shown that the ADRE-AR in the adrenomedullin gene promoter is responsible for the suppression of the adrenomedullin expression, and the Sp1 binding site is for the induction. Furthermore, Sp1 and AP-2 may for the complex, which acts on the gene promoter and stimulate the induction of the adrenomedullin gene expression.
Takahashi ed. al. developed a specific radioimmunoassay for adrenomedullin 2, a novel adrenomedullin-related peptide. Takahashi ed. al. have shown the expression of adrenomedullin in the brain including hypothalamus, pituitary, heart, kidney and adrenal gland. Particularly high concentrations of adrenomedullin 2 were found in the pituitary and kidney. Immunocytochemical studies have shown that adrenomedullin 2 is expressed in the pericardial adipose tissue. Adrenomedullin and adrenomedullin 2 were expressed in the adrenal gland and adrenal tumors, suggesting that these two peptides are involved in the pathophysiology of adrenal tumors. We have obtained data which suggest that a certain gene polymorphysm of the adrenomedullin 2 gene is associated with the occurrence of hypertension in the Ohasama study.
Adrenomedullins secreted by adipocytes may protect the complications of the metabolic syndrome. We hope to continue to study adrenomedullins in the adipocyte in order to develop a novel strategy for obesity, hypertension and diabetes mellitus.
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