scholarly journals Identification of a Novel Na+-independent Acidic Amino Acid Transporter with Structural Similarity to the Member of a Heterodimeric Amino Acid Transporter Family Associated with Unknown Heavy Chains

2002 ◽  
Vol 277 (23) ◽  
pp. 21017-21026 ◽  
Author(s):  
Hirotaka Matsuo ◽  
Yoshikatsu Kanai ◽  
Ju Young Kim ◽  
Arthit Chairoungdua ◽  
Do Kyung Kim ◽  
...  
2021 ◽  
Vol 22 (4) ◽  
pp. 1707
Author(s):  
Sebastian Granitzer ◽  
Raimund Widhalm ◽  
Martin Forsthuber ◽  
Isabella Ellinger ◽  
Gernot Desoye ◽  
...  

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.


2013 ◽  
Vol 34 (2-3) ◽  
pp. 108-120 ◽  
Author(s):  
Yoshikatsu Kanai ◽  
Benjamin Clémençon ◽  
Alexandre Simonin ◽  
Michele Leuenberger ◽  
Martin Lochner ◽  
...  

2001 ◽  
Vol 276 (20) ◽  
pp. 17221-17228 ◽  
Author(s):  
Do Kyung Kim ◽  
Yoshikatsu Kanai ◽  
Arthit Chairoungdua ◽  
Hirotaka Matsuo ◽  
Seok Ho Cha ◽  
...  

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