scholarly journals SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology

Cell Reports ◽  
2019 ◽  
Vol 26 (10) ◽  
pp. 2792-2804.e6 ◽  
Author(s):  
Anna R. Malik ◽  
Kinga Szydlowska ◽  
Karolina Nizinska ◽  
Antonino Asaro ◽  
Erwin A. van Vliet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Functional Expression ◽  
Amino Acid Transporter ◽  
Acid Transporter

scholarly journals SorCS2 controls functional expression of amino acid transporter EAAT3 to protect neurons from oxidative stress and epilepsy-induced pathology

2018 ◽  
Author(s):  
Anna R. Malik ◽  
Kinga Szydlowska ◽  
Karolina Nizinska ◽  
Antonino Asaro ◽  
Erwin A. van Vliet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Amino Acid ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Functional Expression ◽  
Amino Acid Transporter ◽  
Protective Role ◽  
The Family ◽  
Acid Transporter

SUMMARYThe family of VPS10P domain receptors emerges as central regulator of intracellular protein sorting in neurons with relevance for various brain pathologies. Here, we identified a unique role for the family member SorCS2 in protection of neurons from oxidative stress and from epilepsy-induced cell death. We show that SorCS2 acts as sorting receptor that targets the neuronal amino acid transporter EAAT3 to the plasma membrane to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Absence of SorCS2 activity causes aberrant transport of EAAT3 to lysosome for catabolism and impairs cysteine uptake. As a consequence, SorCS2-deficient mice exhibit oxidative brain damage that coincides with enhanced neuronal cell death and increased mortality during epilepsy. Our findings highlight a protective role for SorCS2 in neuronal stress response and provide an explanation for upregulation of the receptor seen in surviving neurons of the human epileptic brain.

scholarly journals Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

2021 ◽  
Vol 22 (4) ◽  
pp. 1707
Author(s):  
Sebastian Granitzer ◽  
Raimund Widhalm ◽  
Martin Forsthuber ◽  
Isabella Ellinger ◽  
Gernot Desoye ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
De Novo ◽  
Structural Similarity ◽  
Amino Acid Transporter ◽  
Cell Number ◽  
Mehg Exposure ◽  
Acid Transporter ◽  
And Oxidative Stress

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

scholarly journals Cloning, functional expression and dietary regulation of the mouse neutral and basic amino acid transporter (NBAT)

1997 ◽  
Vol 328 (2) ◽  
pp. 657-664 ◽  
Author(s):  
Hiroko SEGAWA ◽  
Ken-ichi MIYAMOTO ◽  
Yoshio OGURA ◽  
Hiromi HAGA ◽  
Kyoko MORITA ◽  
...  
Keyword(s):  
Amino Acid ◽  
Xenopus Oocytes ◽  
Physiological Role ◽  
Basic Amino Acid ◽  
Functional Expression ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Transport Activity ◽  
Acid Transporter ◽  
Mouse Ileum

The Na+-independent dibasic and neutral amino acid transporter NBAT is among the least hydrophobic of mammalian amino acid transporters. The transporter contains one to four transmembrane domains and induces amino acid transport activity via a b0,+-like system when expressed in Xenopus oocytes. However, the physiological role of NBAT remains unclear. Complementary DNA clones encoding mouse NBAT have now been isolated. The expression of mouse NBAT in Xenopus oocytes also induced an obligatory amino acid exchange activity similar to that of the b0,+-like system. The amount of NBAT mRNA in mouse kidney increased during postnatal development, consistent with the increase in renal cystine and dibasic transport activity. Dietary aspartate induced a marked increase in cystine transport via the b0,+ system in mouse ileum. A high-aspartate diet also increased the amount of NBAT mRNA in mouse ileum. In the ileum of mice fed on the aspartate diet, the extent of cystine transport was further increased by preloading brush border membrane vesicles with lysine. Hybrid depletion of NBAT mRNA from ileal polyadenylated RNA revealed that the increase in cystine transport activity induced by the high-aspartate diet, as measured in Xenopus oocytes, was attributable to NBAT. These results demonstrate that mouse NBAT has an important role in cystine transport.

Cloning and Functional Expression of ATA1, a Subtype of Amino Acid Transporter A, from Human Placenta

2000 ◽  
Vol 273 (3) ◽  
pp. 1175-1179 ◽  
Author(s):  
Haiping Wang ◽  
Wei Huang ◽  
Mitsuru Sugawara ◽  
Lawrence D. Devoe ◽  
Frederick H. Leibach ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Placenta ◽  
Functional Expression ◽  
Amino Acid Transporter ◽  
Acid Transporter
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