PMID- 18987252
OWN - NLM
STAT- MEDLINE
DCOM- 20090226
LR  - 20230411
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 1
DP  - 2009 Jan
TI  - Regulation of placental amino acid transporter activity by mammalian target of 
      rapamycin.
PG  - C142-50
LID - 10.1152/ajpcell.00330.2008 [doi]
AB  - The activity of placental amino acid transporters is decreased in intrauterine 
      growth restriction (IUGR), but the underlying regulatory mechanisms have not been 
      established. Inhibition of the mammalian target of rapamycin (mTOR) signaling 
      pathway has been shown to decrease the activity of the system L amino acid 
      transporter in human placental villous fragments, and placental mTOR activity is 
      decreased in IUGR. In the present study, we used cultured primary trophoblast 
      cells to study mTOR regulation of placental amino acid transporters in more 
      detail and to test the hypothesis that mTOR alters amino acid transport activity 
      by changes in transporter expression. Inhibition of mTOR by rapamycin 
      significantly reduced the activity of system A (-17%), system L (-28%), and 
      taurine (-40%) amino acid transporters. mRNA expression of isoforms of the three 
      amino acid transporter systems in response to mTOR inhibition was measured using 
      quantitative real-time PCR. mRNA expression of l-type amino acid transporter 1 
      (LAT1; a system L isoform) and taurine transporter was reduced by 13% and 50%, 
      respectively; however, mTOR inhibition did not alter the mRNA expression of 
      system A isoforms (sodium-coupled neutral amino acid transporter-1, -2, and -4), 
      LAT2, or 4F2hc. Rapamycin treatment did not significantly affect the protein 
      expression of any of the transporter isoforms. We conclude that mTOR signaling 
      regulates the activity of key placental amino acid transporters and that this 
      effect is not due to a decrease in total protein expression. These data suggest 
      that mTOR regulates placental amino acid transporters by posttranslational 
      modifications or by affecting transporter translocation to the plasma membrane.
FAU - Roos, S
AU  - Roos S
AD  - Perinatal Center, Department of Physiology, Institute of Neuroscience and 
      Physiology, University of Gothenburg, PO Box 432, Gothenburg SE-405 30, Sweden. 
      sara.roos@gu.se
FAU - Kanai, Y
AU  - Kanai Y
FAU - Prasad, P D
AU  - Prasad PD
FAU - Powell, T L
AU  - Powell TL
FAU - Jansson, T
AU  - Jansson T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081105
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Amino Acid Transport System A)
RN  - 0 (Amino Acid Transport System L)
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 148686-53-7 (taurine transporter)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Amino Acid Transport System A/metabolism
MH  - Amino Acid Transport System L/metabolism
MH  - Amino Acid Transport Systems/genetics/*metabolism
MH  - Apoptosis
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Transport Proteins/metabolism
MH  - Pregnancy
MH  - Protein Kinases/drug effects/*metabolism
MH  - Protein Processing, Post-Translational
MH  - Protein Transport
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
MH  - Trophoblasts/drug effects/*metabolism
EDAT- 2008/11/07 09:00
MHDA- 2009/02/27 09:00
CRDT- 2008/11/07 09:00
PHST- 2008/11/07 09:00 [pubmed]
PHST- 2009/02/27 09:00 [medline]
PHST- 2008/11/07 09:00 [entrez]
AID - 00330.2008 [pii]
AID - 10.1152/ajpcell.00330.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Jan;296(1):C142-50. doi: 
      10.1152/ajpcell.00330.2008. Epub 2008 Nov 5.