Culture in 10% O2 enhances the production of active hormones in neuro-endocrine cells by up-regulating the expression of processing enzymes
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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培养%20in%2010%%20O2%20增强%20the%20产量%20of%20活性%20激素%20in%20神经内分泌%20细胞%20by%20上调%20the%20表达%20of%20处理%20酶
DOI：
10.1042/bcj20180832
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hosaka M
中科院分区：
文献类型：
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作者：
Sato E;Maeda Y;Sato Y;Hinata A;Gomi H;Koga D;Torii S;Watanabe T;Hosaka M
为了模拟生理条件，低氧培养已被用于干细胞和癌症研究。虽然组织内的氧气浓度通常远低于环境的21% O2（范围从3.6到12.8% O2），但大多数细胞培养维持在21% O2。为了阐明o2培养浓度对神经内分泌细胞多肽激素分泌调控的影响，我们检测了在较低o2浓度培养的神经内分泌细胞系和内分泌组织中多肽激素的储存和释放变化。小鼠垂体前叶和新鲜制备的小鼠垂体at -20细胞在10% O2环境中培养24 h后，成熟肽促肾上腺皮质激素的储存和调节分泌量均明显高于21% O2环境中培养的细胞和垂体，而其前体促肾上腺皮质激素原素在10% O2环境中培养后的细胞和组织中未增加。同时，在10% O2条件下培养的细胞中，原激素加工酶PC1/3和羧肽酶E表达上调，促进了原激素向活性形式的转化。同样，在10%的o2中培养小鼠β细胞系MIN6和胰岛组织也显著增加了胰岛素原向成熟胰岛素的转化，并以受调节的方式分泌。以上结果表明，与21% O2环境相比，10% O2环境下的培养更有利于内分泌组织/细胞有效地产生和分泌活性肽激素。
To closely mimic physiological conditions, low oxygen cultures have been employed in stem cell and cancer research. Althoughin vivooxygen 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 O2culture 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 O2concentration. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured in 10% O2for 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% O2also significantly increased the conversion of proinsulin into mature insulin, which was secreted in a regulated manner. These results suggest that culture under 10% O2is more optimal for endocrine tissues/cells to efficiently generate and secrete active peptide hormones than ambient 21% O2.