Journal
BIOCHEMICAL JOURNAL
Volume 476, Issue -, Pages 827-842Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20180832
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Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology [JP25440052, JP18K05443]
- Joint Research Program of the Institute for Molecular and Cellular Regulation, Gunma University [18011]
- Akita Prefectural University President's Research Project Fund
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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% O-2 (ranging from 3.6 to 12.8% O-2), most cell cultures are maintained at 21 % O-2. To clarify the effects of the O-2 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 O-2 concentration. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured in 10% O(2 )for 24 h, the storage and regulated secretion of the mature peptide hormone adrenocorticotropic hormone were significantly increased compared with those in cells arid pituitaries cultured in ambient 21% O-2, whereas its precursor proopiomelanocortin was not increased in the cells and tissues after being cultured in 10% O-2. Simultaneously, the prohormone-processing enzymes PC1/3 and carboxypeptidase E were up-regulated in cells cultured in 10% O-2, thus facilitating the conversion of prohormones to their active form. Similarly, culturing the mouse (3-cell line MIN6 and islet tissue in 10% O(2 )also significantly increased the conversion of proinsulin into mature insulin, which was secreted in a regulated manner. These results suggest that culture under 10% O-2 is more optimal for endocrine tissues/cells to efficiently generate and secrete active peptide hormones than ambient 21 % O-2.
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