Expression of Glutamate Transporters in Mouse Liver, Kidney, and Intestine

Abstract

Glutamate transport activities have been identified not only in the brain, but also in the liver, kidney, and intestine. Although glutamate transporter distributions in the central nervous system are fairly well known, there are still uncertainties with respect to the distribution of these transporters in peripheral organs. Quantitative information is mostly lacking, and few of the studies have included genetically modified animals as specificity controls. The present study provides validated qualitative and semi-quantitative data on the excitatory amino acid transporter (EAAT)1-3 subtypes in the mouse liver, kidney, and intestine. In agreement with the current view, we found high EAAT3 protein levels in the brush borders of both the distal small intestine and the renal proximal tubules. Neither EAAT1 nor EAAT2 was detected at significant levels in murine kidney or intestine. In contrast, the liver only expressed EAAT2 (but 2 C-terminal splice variants). EAAT2 was detected in the plasma membranes of perivenous hepatocytes. These cells also expressed glutamine synthetase. Conditional deletion of hepatic EAAT2 did neither lead to overt neurological disturbances nor development of fatty liver.

Acute Liver Toxicity Modifies Protein Expression of Glutamate Transporters in Liver and Cerebellar Tissue

“…To shed some light on this issue, we analyzed the protein expression of both GLAST/EAAT1 and GLT-1/EAAT2 in liver tissue after CCl 4 treatment. The results described above revealed that as previously reported, GLT-1/EAAT2 is the main Glu transporter expressed in mouse liver (Utsunomiya-Tate et al, 1997;Berger and Hediger, 2006;Hu et al, 2018). The detection of GLT-1/ EAAT2 as several bands in CNS (∼70,150,and 190 kDa) and only one band in liver tissue (∼150 kDa) indicates that this higher molecular weight band might be corresponding to a multimeric fraction of the transporter.…”

“…GLT-1/EAAT2 expression has been reported in rat and mouse liver tissues (Berger and Hediger, 2006;Hu et al, 2018) and recently GLAST/EAAT1 was also reported in a human hepatoblastoma cell line, HepG2 (Jiménez-Torres et al, 2020). FIGURE 2 | slices by immunohistochemistry using the same antibody as in western blot analyses.…”

“…The disruption of the activity and expression of GS and the two main Glu transporters in the Central Nervous System (CNS), the Na + -dependent Glu and aspartate transporter (GLAST/EAAT1) and Glu transporter1 (GLT-1/EAAT2) have been described in advanced liver injuries such as HE and hyperammonemia (Waniewski, 1992;Butterworth, 2002;Bémeur and Butterworth, 2013;Hu et al, 2018;Sohn et al, 2018). However, the effects on Glu transporters expression at early stages of liver injury are poorly characterized.…”

Glutamate in cancers: from metabolism to signaling

“…EAATs are also found in peripheral tissues; for instance, EAAT3, originally known as EAAC1, was reported to have mRNA expressed in the liver, the intestine, the kidney and the heart of rabbits [ 14 ] . Lately, a low level of EAAT1 mRNA was identified in the mouse liver, kidney and intestine, with relatively a little higher EAAT2 in the liver, much higher EAAT3 at intestine and highest EAAT3 in the kidney [ 88 ] . Moreover, broad expression of EAAT5 in the liver, kidney, intestine, heart, lung and skeletal muscle of rats has been identified at both mRNA and protein levels [ 89 ] .…”

Neuronal excitatory amino acid transporter EAAT3: Emerging functions in health and disease

“…Cysteine is the rate-limiting substrate for the synthesis of the antioxidant glutathione and its extracellular depletion is hypothesized to contribute to neurodegeneration. EAAT3 is also the dominant glutamate transporter in the intestines and provides nutrient absorption from the diet (Hu et al, 2018), but knockout animals appear to grow at a comparable rate to their litter mates (Peghini et al, 1997). The most remarkable initial observation from EAAT3 knockout mice was aminoaciduria due to the absence of EAAT3 in the kidneys (Peghini et al, 1997).…”