Characterization and regulation of the gene expression of amino acid transport system A (SNAT2) in rat mammary gland.
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.
López
Adriana
A
Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Torres
Nimbe
N
Ortiz
Victor
V
Alemán
Gabriela
G
Hernández-Pando
Rogelio
R
Tovar
Armando R
AR
D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems / Q000235:genetics* / Q000378:metabolism*; D021542:Amino Acids, Neutral / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D020871:RNA Stability / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D021542:Amino Acids, Neutral; D004791:Enzyme Inhibitors; C412568:Slc38a2 protein, rat; D011374:Progesterone; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C