| Project/Area Number |
18K05443
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38030:Applied biochemistry-related
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| Research Institution | Akita Prefectural University |
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Principal Investigator |
Hosaka Masahiro 秋田県立大学, 生物資源科学部, 教授 (80311603)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 内分泌細胞 / 酸素応答 / プロセッシング酵素 / ペプチドホルモン / 分泌顆粒 |
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| Outline of Final Research Achievements |
Although in vivo oxygen concentrations in tissues are often much lower than ambient 21% oxygen (ranging from 3.6 to 12.8% oxygen), most cell cultures are maintained at 21% oxygen. We examined the changes in the storage and release of peptide hormones in endocrine cell lines and tissues cultured at relatively lower oxygen. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured at 10% oxygen for 24 h, storage and regulated secretion of the mature peptide hormone adrenocorticotropic hormone were significantly increased compared with those cultured at ambient 21% oxygen, whereas its precursor proopiomelanocortin was not increased in the cells and tissues after 10% oxygen culture. Simultaneously, the prohormone processing enzymes PC1/3 and carboxypeptidase E were up-regulated in cells cultured at 10% oxygen, thus facilitating conversion of prohormones to their active form. Similar effects were also observed in insulin secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
生体組織における酸素濃度では大気中と比較して低く 3.6-12.8％である。本研究で生理的酸素濃度下でのホルモン分泌能を調べたところ、ペプチドホルモンを分泌顆粒で修飾するプロセッシング酵素群の発現が亢進し、成熟型ホルモンの細胞内貯蔵量と分泌が最大値となることを見出した。我々は本研究での発見が内分泌機能調節系固有の酸素応答の分子機構について、細胞から個体レベルまで広範囲にわたる新たな知見を加えることができたと考えている。
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