Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo)
Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo)
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DOI：
10.1152/ajpendo.00359.2005
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发表时间：
2006-09-01
影响因子：
5.1
通讯作者：
McArdle, Harry J.
中科院分区：
文献类型：
--
作者：
Jones, Helen N.;Ashworth, Cheryl J.;McArdle, Harry J.
胎盘系统 A 活性和胎儿血浆皮质醇浓度均与宫内生长迟缓相关，但尚不清楚这些因素是否在机制上相关。先前使用肝癌细胞和成纤维细胞进行的功能研究在皮质醇对系统 A 的调节方面产生了相互矛盾的结果。使用 b30 BeWo 绒毛膜癌细胞系，我们研究了皮质醇对系统 A 的调节。使用甲基氨基异丁酸 (MeAIB) 跨细胞转运研究分析系统 A 功能。分别使用 Northern 和 Western blotting 在 mRNA 和蛋白质水平上研究转运蛋白表达 [ 系统 A 转运蛋白 (SNAT)1/2]。使用免疫细胞化学进行定位。与对照相比，与皮质醇预孵育 24 小时后，[C-14] MeAIB 跨 BeWo 单层的转移率显着增加。这与皮质醇水平较低时 SNAT2 转运蛋白的重新定位以及皮质醇水平 > 1 muM 时 mRNA 和蛋白质表达水平的显着上调有关。这是第一项显示 BeWo 细胞中皮质醇对系统 A 的功能和分子调节的研究。这也是第一项确定哪种系统 A 同工型受到调节的研究。这些结果表明皮质醇可能参与胎盘中 A 系统的上调，以确保发育中的胎儿有足够的氨基酸供应。
Both placental system A activity and fetal plasma cortisol concentrations are associated with intrauterine growth retardation, but it is not known if these factors are mechanistically related. Previous functional studies using hepatoma cells and fibroblasts produced conflicting results regarding the regulation of system A by cortisol. Using the b30 BeWo choriocarcinoma cell line, we investigated the regulation of system A by cortisol. System A function was analyzed using methyl amino isobutyric acid ( MeAIB) transcellular transport studies. Transporter expression [ system A transporter (SNAT)1/2] was studied at the mRNA and protein levels using Northern and Western blotting, respectively. Localization was carried out using immunocytochemistry. The [C-14] MeAIB transfer rate across BeWo monolayers after preincubation with cortisol for 24 h was significantly increased compared with control. This was associated with a relocalization of the SNAT2 transporter at lower cortisol levels and significant upregulation of mRNA and protein expression levels at cortisol levels > 1 mu M. This is the first study to show functional and molecular regulation of system A by cortisol in BeWo cells. It is also the first study to identify which system A isoform is regulated. These results suggest that cortisol may be involved in upregulation of system A in the placenta to ensure sufficient amino acid supply to the developing fetus.