Disease relevance of SLC38A2

• Synthesis of SNAT2 mRNA increased within 1-2 h after amino acid removal from HepG2 human hepatoma cells [1].
• Hypoxia decreased expression of hATA1 and hATA2 in both trophoblast phenotypes [2].
• Correlation between GM3/GD3 ratio and SAT-2 activity; (2), mammary carcinomas developed in MMTV/c-neu transgenic mice: accumulation of GM3-derived species [3].
• The different ganglioside distribution seems to correlate with the tumour size; (3), Sarcoma Galliera-strain cells SGS/3A and normal syngenic murine fibroblasts FG: transformed cells exhibit a lower activity of sialyltransferases (SAT-1, SAT-2, SAT-4) compared to normal fibroblasts, suggesting a possible correlation with the ganglioside pattern [3].

High impact information on SLC38A2

• In contrast, the response to hypertonic stress does not involve eukaryotic initiation factor 2alpha phosphorylation, suggesting that SNAT2 expression can be modulated by specific signaling pathways in response to different stresses [4].
• We also show that amino acid starvation caused a 2.5-fold increase in mRNA and protein expression from a reporter construct containing both the SNAT2 intronic amino acid response element and the SNAT2-untranslated region [4].
• System A amino acid transporter (SNAT2) gene expression is up-regulated at the transcriptional level in response to amino acid deprivation [5].
• Functional analysis of genomic fragments 5' upstream of the transcription start site, for both human and mouse SNAT2 genes showed that these regions exhibit promoter activity, but were amino acid unresponsive [5].
• The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter [5].

Biological context of SLC38A2

• Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene [1].
• It is concluded that the up-regulation of SNAT2 is essential for the rapid restoration of cell volume after hypertonic stress [6].
• In hypertonically stressed human fibroblasts transfection with two siRNAs for SNAT2 suppressed the increase in SNAT2 mRNA and the stimulation of system A transport activity [6].
• Amino acid depletion was associated with an up-regulation of SysA activity, largely mediated through an enhancement of SNAT2 (Slc38a2) expression at both the protein and mRNA level [7].
• System A, the Na(+)-dependent amino acid transport activity, is encoded by the ATA2 gene and up-regulated following partial hepatectomy (PH), and its competitive inhibition interferes with liver regeneration [8].

Anatomical context of SLC38A2

• Fibroblasts that are deficient in the amino acid response pathway exhibited little or no induction of SNAT2 mRNA [1].
• When expressed in Xenopus laevis oocytes, transport of neutral amino acids via ATA2 is associated with inward currents [9].
• This transporter, designated ATA2 for amino acid transporter A2, was cloned from rat skeletal muscle [9].
• ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane [8].
• This transporter, designated ATA2 for amino acid transporter A2, was cloned from the human hepatoma cell line HepG2 [10].

Associations of SLC38A2 with chemical compounds

• On the contrary, if the transport activity of system A is adaptively increased by amino acid starvation in the presence of DRB, the increase of SNAT2 transporters on the plasma membrane is still clearly detectable and the transport change only partially inhibited [11].
• We show that slices from injured cortex take up glutamine more readily than control slices, and an increased expression of the system A transporters SNAT1 and SNAT2 likely underlies this difference [12].
• Photolytic release of free alanine results in the generation of significant transient current components in HEK293 cells expressing the ASCT2, SNAT1, and SNAT2 proteins [13].
• Furthermore, in contrast to AS, transcription from the ATA2 gene was not increased by glucose deprivation [14].
• Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo) [15].

Other interactions of SLC38A2

• Chromatin immunoprecipitation analysis established in vivo that amino acid deprivation led to increased RNA polymerase II recruitment to the SNAT2 promoter [1].
• Our findings support a role for glutamine transport through SNAT1 and/or SNAT2 in the maintenance of abnormal activity in this in vitro model of epileptogenesis and suggest that system A transport and glutamine metabolism are potential targets for pharmacological intervention in seizures and epilepsy [12].
• 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 [16].

Analytical, diagnostic and therapeutic context of SLC38A2

• The increased level of SNAT2 transporters in hypertonically stressed cells is confirmed by immunocytochemistry [11].
• However, the results of our confocal and electron microscopy immunocytochemical studies of the localization of these transporters in the cerebral cortex show that SNAT1 and SNAT2 are robustly expressed in the somatodendritic domain of cortical neurons, but rarely to axon terminals [17].
• OBJECTIVE: To compare the clinical performance of three pulmonary artery oximetry catheters (Oximetrix 3, SAT-2, and HEMOPRO2) in intensive care unit (ICU) patients [18].
• Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization [19].

References