López Adriana, Torres Nimbe, Ortiz Victor, Alemán Gabriela, Hernández-Pando Rogelio, Tovar Armando R
Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1059-66. doi: 10.1152/ajpendo.00062.2006. Epub 2006 Jun 20.
Amino acid transport via system A plays an important role during lactation, promoting the uptake of small neutral amino acids, mainly alanine and glutamine. However, the regulation of gene expression of system A [sodium-coupled neutral amino acid transporter (SNAT)2] in mammary gland has not been studied. The aim of the present work was to understand the possible mechanisms of regulation of SNAT2 in the rat mammary gland. Incubation of gland explants in amino acid-free medium induced the expression of SNAT2, and this response was repressed by the presence of small neutral amino acids or by actinomycin D but not by large neutral or cationic amino acids. The half-life of SNAT2 mRNA was 67 min, indicating a rapid turnover. In addition, SNAT2 expression in the mammary gland was induced by forskolin and PMA, inducers of PKA and PKC signaling pathways, respectively. Inhibitors of PKA and PKC pathways partially prevented the upregulation of SNAT2 mRNA during adaptive regulation. Interestingly, SNAT2 mRNA was induced during pregnancy and to a lesser extent at peak lactation. beta-Estradiol stimulated the expression of SNAT2 in mammary gland explants; this stimulation was prevented by the estrogen receptor inhibitor ICI-182780. Our findings clearly demonstrated that the SNAT2 gene is regulated by multiple pathways, indicating that the expression of this amino acid transport system is tightly controlled due to its importance for the mammary gland during pregnancy and lactation to prepare the gland for the transport of amino acids during lactation.
通过A系统进行的氨基酸转运在泌乳过程中发挥着重要作用，促进主要为丙氨酸和谷氨酰胺的小中性氨基酸的摄取。然而，乳腺中A系统[钠偶联中性氨基酸转运体（SNAT）2]的基因表达调控尚未得到研究。本研究的目的是了解大鼠乳腺中SNAT2的可能调控机制。将腺体外植体在无氨基酸培养基中孵育可诱导SNAT2的表达，这种反应会被小中性氨基酸的存在或放线菌素D抑制，但不会被大中性或阳离子氨基酸抑制。SNAT2 mRNA的半衰期为67分钟，表明其周转迅速。此外，乳腺中SNAT2的表达分别被福斯可林和PMA诱导，它们分别是PKA和PKC信号通路的诱导剂。PKA和PKC通路的抑制剂在适应性调节过程中部分阻止了SNAT2 mRNA的上调。有趣的是，SNAT2 mRNA在怀孕期被诱导，在泌乳高峰期诱导程度较小。β-雌二醇刺激乳腺外植体中SNAT2的表达；雌激素受体抑制剂ICI-182780可阻止这种刺激。我们的研究结果清楚地表明，SNAT2基因受多种途径调控，这表明由于该氨基酸转运系统在怀孕和泌乳期间对乳腺为泌乳期氨基酸转运做准备的重要性，其表达受到严格控制。
