Promoter characterization and role of CRE in the basal transcription of the rat SNAT2 gene

Ortíz, Víctor; Alemán, Gabriela; Escamilla-Del-Arenal, Martín; Recillas‐Targa, Félix; Torres, Nimbe; Tovar, Armando R.

doi:10.1152/ajpendo.00459.2010

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…Urea nitrogen also increased, suggesting that glucagon may indirectly regulate amino acid levels through regulation of gluconeogenesis [224]. In agreement with this notion, glucagon also increases transcription of Sodium-neutral amino acid transporter SNAT2 in hepatocytes through a cAMP response element in the promoter region [225]. …”

Section: Systemic Amino Acid Homeostasismentioning

confidence: 87%

Amino acid homeostasis and signalling in mammalian cells and organisms

Bröer

2017

Biochemical Journal

399

340

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Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids. Metabolism is autoregulated to minimise oxidation of amino acids. Systemic amino acid levels are also tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Excess amino acids are oxidised, resulting in increased urea production. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. Owing to the fact that half of all amino acids are essential, reduction in protein synthesis and amino acid oxidation are the only two measures to reduce amino acid demand. Long-term malnutrition causes depletion of plasma amino acids. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. High protein levels, in contrast, contribute together with other nutrients to a reduction in food intake.

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Section: Systemic Amino Acid Homeostasismentioning

confidence: 87%

Amino acid homeostasis and signalling in mammalian cells and organisms

Bröer

2017

Biochemical Journal

399

340

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“…For SNAT2, a regulation by amino acid deprivation has been described and the mechanism linked to the presence in the first intron of a amino acid response element (AARE) acting as enhancer (Palii et al, 2004). Moreover, in liver SNAT2 is up-regulated by glucagon (Ortiz et al, 2011). For SNAT3 a regulation by PKC has been reported and linked to the glutamate/GABA-glutamine of the central nervous system.…”

Section: Slc38: Snatsmentioning

confidence: 99%

Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health

et al. 2014

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Glutamine together with glucose is essential for body's homeostasis. It is the most abundant amino acid and is involved in many biosynthetic, regulatory and energy production processes. Several membrane transporters which differ in transport modes, ensure glutamine homeostasis by coordinating its absorption, reabsorption and delivery to tissues. These transporters belong to different protein families, are redundant and ubiquitous. Their classification, originally based on functional properties, has recently been associated with the SLC nomenclature. Function of glutamine transporters is studied in cells over-expressing the transporters or, more recently in proteoliposomes harboring the proteins extracted from animal tissues or over-expressed in microorganisms. The role of the glutamine transporters is linked to their transport modes and coupling with Na+ and H+. Most transporters share specificity for other neutral or cationic amino acids. Na+-dependent co-transporters efficiently accumulate glutamine while antiporters regulate the pools of glutamine and other amino acids. The most acknowledged glutamine transporters belong to the SLC1, 6, 7, and 38 families. The members involved in the homeostasis are the co-transporters B0AT1 and the SNAT members 1, 2, 3, 5, and 7; the antiporters ASCT2, LAT1 and 2. The last two are associated to the ancillary CD98 protein. Some information on regulation of the glutamine transporters exist, which, however, need to be deepened. No information at all is available on structures, besides some homology models obtained using similar bacterial transporters as templates. Some models of rat and human glutamine transporters highlight very similar structures between the orthologs. Moreover the presence of glycosylation and/or phosphorylation sites located at the extracellular or intracellular faces has been predicted. ASCT2 and LAT1 are over-expressed in several cancers, thus representing potential targets for pharmacological intervention.

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“…Therefore, the supply of amino acids is significantly increased when rats consumed a high protein diet as has been previously reported [33]. It has been demonstrated that an increase in the amount of dietary protein, stimulates the serum glucagon levels, which in turn upregulates the expression of SNAT2 via PKA in the liver, since the SNAT2 promoter gene contains a cAMP response element (CRE) at −48 bp [30].…”

Section: Discussionmentioning

confidence: 79%

“…Our results also demonstrated that the dietary protein/carbohydrate ratio influences the serum prolactin concentration. This may imply that the reduction of prolactin decreases SNAT2 expression or that the dietary protein/carbohydrate ratio can directly modulate the expression of this gene possibly via cAMP, as has been reported in the liver [30]. Further studies are needed to dissect this mechanism.…”

Section: Discussionmentioning

confidence: 91%

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation

Velázquez-Villegas

López-Barradas

Torres

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The sodium coupled neutral amino acid transporter 2 (SNAT2/SAT2/ATA2) is expressed in the mammary gland (MG) and plays an important role in the uptake of alanine and glutamine which are the most abundant amino acids transported into this tissue during lactation. Thus, the aim of this study was to assess the amount and localization of SNAT2 before delivery and during lactation in rat MG, and to evaluate whether prolactin and the dietary protein/carbohydrate ratio might influence SNAT2 expression in the MG, liver and adipose tissue during lactation. Our results showed that SNAT2 protein abundance in the MG increased during lactation and this increase was maintained along this period, while 24 h after weaning it tended to decrease. To study the effect of prolactin on SNAT2 expression, we incubated MG explants or T47D cells transfected with the SNAT2 promoter with prolactin, and we observed in both studies an increase in the SNAT2 expression or promoter activity. Consumption of a high-protein/low carbohydrate diet increased prolactin concentration, with a concomitant increase in SNAT2 expression not only in the MG during lactation, but also in the liver and adipose tissue. There was a correlation between SNAT2 expression and serum prolactin levels depending on the amount of dietary protein/carbohydrate ratio consumed. These findings suggest that prolactin actively supports lactation providing amino acids to the gland through SNAT2 for the synthesis of milk proteins.

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Promoter characterization and role of CRE in the basal transcription of the rat SNAT2 gene

Cited by 16 publications

References 39 publications

Amino acid homeostasis and signalling in mammalian cells and organisms

Amino acid homeostasis and signalling in mammalian cells and organisms

Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation

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