PMID- 17646425
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20191210
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 72
IP  - 5
DP  - 2007 Nov
TI  - Regulation of glutathione synthesis via interaction between glutamate 
      transport-associated protein 3-18 (GTRAP3-18) and excitatory amino acid carrier-1 
      (EAAC1) at plasma membrane.
PG  - 1103-10
AB  - Regulation of the cysteine transporter known as excitatory amino acid carrier-1 
      (EAAC1) for intracellular glutathione (GSH) content was investigated using human 
      embryonic kidney (HEK) 293 cells as a model system. GSH content was significantly 
      reduced by l-aspartate-beta-hydroxamate (50-250 microM), an inhibitor of both 
      EAAC1 and GLT1, both of which are transporters to take up cysteine, whereas 
      dihydrokainate (1-100 microM), a specific inhibitor of GLT1, failed to do so. 
      This indicates that EAAC1 is involved in GSH content in HEK293 cells. We examined 
      the effect of glutamate transport-associated protein 3-18 (GTRAP3-18), which is 
      capable of interacting with EAAC1. The GSH content decreased when the GTRAP3-18 
      protein level at the plasma membrane was increased by methyl-beta-cyclodextrin 
      (250 microM), rendering the cells more vulnerable to oxidative stress. 
      Intracellular GSH increased when the GTRAP3-18 protein level at the plasma 
      membrane was decreased by antisense oligonucleotides, rendering the cells more 
      resistant to oxidative stress. Furthermore, we found that the increase in GSH 
      content produced by stimulating protein kinase C, a translocator and activator of 
      EAAC1, was inhibited by an increase in cell surface GTRAP3-18 protein. These 
      results show GTRAP3-18 to negatively and dominantly regulate cellular GSH content 
      via interaction with EAAC1 at the plasma membrane.
FAU - Watabe, Masahiko
AU  - Watabe M
AD  - Department of Pharmacology, Teikyo University School of Medicine, 2-11-1, Kaga, 
      Itabashi-ku, Tokyo 173-8605, Japan.
FAU - Aoyama, Koji
AU  - Aoyama K
FAU - Nakaki, Toshio
AU  - Nakaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070723
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (ARL6IP5 protein, human)
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (SLC1A1 protein, human)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Cell Line
MH  - Cell Membrane/chemistry/*metabolism
MH  - Excitatory Amino Acid Transporter 3/analysis/genetics/*metabolism
MH  - Glutathione/*biosynthesis
MH  - Heat-Shock Proteins/analysis/genetics/*metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/analysis/genetics/*metabolism
MH  - Membrane Transport Proteins
EDAT- 2007/07/25 09:00
MHDA- 2007/12/14 09:00
CRDT- 2007/07/25 09:00
PHST- 2007/07/25 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/07/25 09:00 [entrez]
AID - mol.107.039461 [pii]
AID - 10.1124/mol.107.039461 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2007 Nov;72(5):1103-10. doi: 10.1124/mol.107.039461. Epub 2007 Jul 
      23.