Culture in 10% O2 enhances the production of active hormones in neuro-endocrine cells by up-regulating the expression of processing enzymes

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  • Eri Sato
    Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan
  • Yoshinori Maeda
    Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan
  • Yui Sato
    Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan
  • Airi Hinata
    Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan
  • Hiroshi Gomi
    Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, Fujisawa 252-0880, Japan
  • Daisuke Koga
    Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa 078-8510, Japan
  • Seiji Torii
    Biosignal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
  • Tsuyoshi Watanabe
    Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa 078-8510, Japan
  • Masahiro Hosaka
    Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan

抄録

<jats:title>Abstract</jats:title> <jats:p>To closely mimic physiological conditions, low oxygen cultures have been employed in stem cell and cancer research. Although in vivo oxygen concentrations in tissues are often much lower than ambient 21% O2 (ranging from 3.6 to 12.8% O2), most cell cultures are maintained at 21% O2. To clarify the effects of the O2 culture concentration on the regulated secretion of peptide hormones in neuro-endocrine cells, we examined the changes in the storage and release of peptide hormones in neuro-endocrine cell lines and endocrine tissues cultured in a relatively lower O2 concentration. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured in 10% O2 for 24 h, the storage and regulated secretion of the mature peptide hormone adrenocorticotropic hormone were significantly increased compared with those in cells and pituitaries cultured in ambient 21% O2, whereas its precursor proopiomelanocortin was not increased in the cells and tissues after being cultured in 10% O2. Simultaneously, the prohormone-processing enzymes PC1/3 and carboxypeptidase E were up-regulated in cells cultured in 10% O2, thus facilitating the conversion of prohormones to their active form. Similarly, culturing the mouse β-cell line MIN6 and islet tissue in 10% O2 also significantly increased the conversion of proinsulin into mature insulin, which was secreted in a regulated manner. These results suggest that culture under 10% O2 is more optimal for endocrine tissues/cells to efficiently generate and secrete active peptide hormones than ambient 21% O2.</jats:p>

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