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Regulation of placental amino acid transporter activity by mammalian target of rapamycin
Abstract
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.
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“In addition, the mTOR pathway regulates the activity of system A, system L and taurine amino acid transporters in the placenta at the post-translational level, either through modifications or by influencing translocation to the apical membrane (469).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [469]
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Cites
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
Boney, C. M., Verma, A., Tucker, R., & Vohr, B. R. (2005) · Pediatrics · doi:10.1542/peds.2004-1808 · Cited by 2,303
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097
Kliman, H. J., Nestler, J. E., SERMASI, E., Sanger, J. M., & Strauss, J. F. (1986) · Endocrinology · doi:10.1210/endo-118-4-1567 · Cited by 1,572
Birth Weight and Adult Hypertension, Diabetes Mellitus, and Obesity in US Men
Curhan, G. C., Willett, W. C., Rimm, E. B., Spiegelman, D. L., Ascherio, A., & Stampfer, M. J. (1996) · Circulation · doi:10.1161/01.cir.94.12.3246 · Cited by 917
Nobukuni, T., Joaquin, M., Roccio, M., Dann, S. G., Kim, S. Y., Gulati, P., Byfield, M. P., Backer, J., Natt, F., Bos, J. L., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506925102 · Cited by 775
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake
Edinger, A. L., & Thompson, C. B. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-12-0584 · Cited by 589
hVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase
Byfield, M. P., Murray, J. T., & Backer, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507201200 · Cited by 539
Pregnancy Outcomes in Women With Gestational Diabetes Compared With the General Obstetric Population
Casey, B. M. (1997) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(97)00542-5 · Cited by 434
Peng, T., Golub, T. R., & Sabatini, D. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5575-5584.2002 · Cited by 404
Yung, H.-W., Calabrese, S., Hynx, D., Hemmings, B. A., Cetin, I., Charnock-Jones, D. S., & Burton, G. J. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.071193 · Cited by 388
Glazier, J. D., Cetin, I., Perugino, G., Ronzoni, S., Grey, A. M., Mahendran, D., Marconi, A. M., Pardi, G., & Sibley, C. P. (1997) · Pediatric Research · doi:10.1203/00006450-199710000-00016 · Cited by 287
Roos, S., Jansson, N., Palmberg, I., Säljö, K., Powell, T. L., & Jansson, T. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.129676 · Cited by 283
Self-citationThe fetal origins of adult disease
Robinson, R. (2001) · BMJ · doi:10.1136/bmj.322.7283.375 · Cited by 272
A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
Findlay, G. M., Yan, L., Procter, J., Mieulet, V., & Lamb, R. F. (2007) · Biochemical Journal · doi:10.1042/bj20061881 · Cited by 267
Jansson, N., Pettersson, J., Haafiz, A., Ericsson, A., Palmberg, I., Tranberg, M., Ganapathy, V., Powell, T. L., & Jansson, T. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.550004 · Cited by 265
Self-citationCetin, I., Corbetta, C., Sereni, L. P., Marconi, A. M., Bozzetti, P., Pardi, G., & Battaglia, F. C. (1990) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(90)90860-a · Cited by 259
The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease
Barker, D. J. (1995) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1995.0173 · Cited by 251
Maiiendran, D., Donnai, P., Glazier, J. D., D'Souza, S. W., Boyd, R. D., & Sibley, C. P. (1993) · Pediatric Research · doi:10.1203/00006450-199311000-00019 · Cited by 247
Current Concepts in Intrauterine Growth Restriction
Brodsky, D. D., & Christou, H. A. (2004) · Journal of Intensive Care Medicine · doi:10.1177/0885066604269663 · Cited by 246
Amino Acid Transporters in the Human Placenta
Jansson, T. (2001) · Pediatric Research · doi:10.1203/00006450-200102000-00003 · Cited by 245
Self-citationJansson, N., Greenwood, S. L., Johansson, B. R., Powell, T. L., & Jansson, T. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021332 · Cited by 243
Self-citationJansson, T., Ekstrand, Y., Björn, C., Wennergren, M., & Powell, T. L. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2214 · Cited by 238
Self-citationPlacental Transport of Leucine and Lysine Is Reduced in Intrauterine Growth Restriction1
Jansson, T., Scholtbach, V., & Powell, T. L. (1998) · Pediatric Research · doi:10.1203/00006450-199810000-00011 · Cited by 235
Self-citationEvaluation of housekeeping genes in placental comparative expression studies
Meller, M., Vadachkoria, S., Luthy, D. A., & Williams, M. A. (2004) · Placenta · doi:10.1016/j.placenta.2004.09.009 · Cited by 229
Peyrollier, K., Hajduch, É., Blair, A. S., Hyde, R., & Hundal, H. S. (2000) · Biochemical Journal · doi:10.1042/bj3500361 · Cited by 210
Norberg, S., Powell, T. L., & Jansson, T. (1998) · Pediatric Research · doi:10.1203/00006450-199808000-00016 · Cited by 203
Self-citationAbnormal Glucose Tolerance During Pregnancy in Pima Indian Women: Long-Term Effects on Offspring
Pettitt, D. J., Bennett, P. H., Saad, M. F., Charles, M.-A. A., Nelson, R. G., & Knowler, W. C. (1991) · Diabetes · doi:10.2337/diab.40.2.s126 · Cited by 194
Management of fetal growth restriction
Alberry, M., & SOOTHILL, P. W. (2006) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/adc.2005.082297 · Cited by 189
Trends in fetal growth among singleton gestations in the United States and Canada, 1985 through 1998
Ananth, C. V., & Wen, S. W. (2002) · Seminars in Perinatology · doi:10.1053/sper.2002.34772 · Cited by 183
The mammalian target of rapamycin regulates lipid metabolism in primary cultures of rat hepatocytes
Brown, N. F., Stefanović-Račić, M., SIPULA, I. J., & Perdomo, G. (2007) · Metabolism · doi:10.1016/j.metabol.2007.06.016 · Cited by 162
Edinger, A. L., Linardic, C. M., Chiang, G. G., Thompson, C. B., & Abraham, R. T. (2003) · PubMed · Cited by 162
Plasma amino acids in appropriate- and small-for-gestational-age fetuses
Economides, D. L., Nicolaides, K. H., Gahl, W. A., Bernardini, I. M., & Evans, M. I. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90670-4 · Cited by 161
Hennig, K. M., Colombani, J., & Neufeld, T. P. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200511140 · Cited by 153
Placental Amino Acid Uptake in Normal and Complicated Pregnancies
Dicke, J. M., & Henderson, G. I. (1988) · The American Journal of the Medical Sciences · doi:10.1097/00000441-198803000-00012 · Cited by 135
SIPULA, I. J., Brown, N. F., & Perdomo, G. (2006) · Metabolism · doi:10.1016/j.metabol.2006.08.002 · Cited by 122
SNAT4 isoform of system A amino acid transporter is expressed in human placenta
Desforges, M., Lacey, H. A., Glazier, J. D., Greenwood, S. L., Mynett, K. J., Speake, P. F., & Sibley, C. P. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00258.2005 · Cited by 114
Karl, P. I. (1995) · Journal of Cellular Physiology · doi:10.1002/jcp.1041650111 · Cited by 112
Nelson, D. M., Smith, S. D., Furesz, T. C., Sadovsky, Y., Ganapathy, V., Parvin, C. A., & Smith, C. H. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00253.2002 · Cited by 112
Amino acid transport by the cultured human placental trophoblast: effect of insulin on AIB transport
Karl, P. I., Alpy, K. L., & Fisher, S. E. (1992) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1992.262.4.c834 · Cited by 109
Kuruvilla, A. G., D'Souza, S. W., Glazier, J. D., Mahendran, D., Maresh, M., & Sibley, C. P. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117386 · Cited by 107
Ling, R., Bridges, C. C., Sugawara, M., Fujita, T., Leibach, F. H., Prasad, P. D., & Ganapathy, V. (2001) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(01)00310-8 · Cited by 107
Self-citationKulanthaivel, P., Cool, D. R., Ramamoorthy, S., Mahesh, V. B., Leibach, F. H., & Ganapathy, V. (1991) · Biochemical Journal · doi:10.1042/bj2770053 · Cited by 89
Ericsson, A., Säljö, K., Sjöstrand, E., Jansson, N., Prasad, P. D., Powell, T. L., & Jansson, T. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.131185 · Cited by 83
Self-citationJones, H. N., Ashworth, C. J., Page, K., & McArdle, H. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00359.2005 · Cited by 83
Regulation of Leucine Uptake by tor1+ in Schizosaccharomyces pombe Is Sensitive to Rapamycin
Weisman, R., Roitburg, I., Nahari, T., & Kupiec, M. (2004) · Genetics · doi:10.1534/genetics.104.034983 · Cited by 81
Ericsson, A., Hamark, B., Jansson, N., Johansson, B. R., Powell, T. L., & Jansson, T. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00407.2004 · Cited by 81
Self-citationRoos, S., Powell, T. L., & Jansson, T. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00232.2004 · Cited by 80
Self-citationExpression and regulation of 4F2hc and hLAT1 in human trophoblasts
Okamoto, Y., Sakata, M., Ogura, K., Yamamoto, T., Yamaguchi, M., Tasaka, K., Kurachi, H., Tsurudome, M., & Murata, Y. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2002.282.1.c196 · Cited by 79
Liu, X., Reyna, S. V., Ensenat, D., Peyton, K. J., Wang, H., Schafer, A. I., & Durante, W. (2004) · The FASEB Journal · doi:10.1096/fj.03-0886fje · Cited by 76
ASC system activity is altered by development of cell polarity in trophoblast from human placenta
Furesz, T. C., Smith, C. H., & Moe, A. J. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.1.c212 · Cited by 62
Jones, H. N., Ashworth, C. J., Page, K., & McArdle, H. J. (2006) · Reproduction · doi:10.1530/rep.1.00808 · Cited by 57
Park, S. Y., Kim, J.-K., Kim, I. J., Choi, B. K., Jung, K. Y., Lee, S., Park, K. J., Chairoungdua, A., Kanai, Y., Endou, H., et al. (2005) · Archives of Pharmacal Research · doi:10.1007/bf02977671 · Cited by 49
Self-citationMagnusson-Olsson, A. L., Lager, S., Jacobsson, B., Jansson, T., & Powell, T. L. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00571.2006 · Cited by 48
Self-citationYusuf, K., Smith, S. D., Sadovsky, Y., & Nelson, D. M. (2002) · Pediatric Research · doi:10.1203/00006450-200209000-00018 · Cited by 46
Jayanthi, L. D., Ramamoorthy, S., Mahesh, V. B., Leibach, F. H., & Ganapathy, V. (1995) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(95)80024-a · Cited by 46
Stimulation of the creatine transporter SLC6A8 by the protein kinase mTOR
Shojaeifard, M. B., Christie, D. L., & Lang, F. J. W. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.055 · Cited by 42
Ramamoorthy, S., Leibach, F. H., Mahesh, V. B., & Ganapathy, V. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90255-a · Cited by 36
Khullar, S., Greenwood, S. L., McCord, N., Glazier, J. D., & Ayuk, P. T.-Y. (2003) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.11.007 · Cited by 33
Inhibition of Amino Acid Transport System A by Interleukin-1β in Trophoblasts
Thongsong, B., Subramanian, R., Ganapathy, V., & Prasad, P. D. (2005) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2005.06.008 · Cited by 33
Self-citationKudo, Y., & Boyd, C. A. R. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00013.x · Cited by 33
Bloxam, D. L., Bax, B. E., & Bax, C. M. R. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1317 · Cited by 32
Stimulation of the intestinal phosphate transporter SLC34A2 by the protein kinase mTOR
Shojaeifard, M. B., & Lang, F. J. W. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.067 · Cited by 30
Selective Impairment of Taurine Transport by Cyclosporin A in a Human Placental Cell Line
Ramamoorthy, S., Leibach, F. H., Mahesh, V. B., & Ganapathy, V. (1992) · Pediatric Research · doi:10.1203/00006450-199207000-00024 · Cited by 29
L-Type Amino Acid Transporter-1 Expressed in Human Astrocytomas, U343MGa
Asano, S., Kameyama, M., Oura, A., Morisato, A., 酒井, 秀., Tabuchi, Y., Chairoungdua, A., Endou, H., & Kanai, Y. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.415 · Cited by 24
Self-citationGrowth factors regulate cell survival by controlling nutrient transporter expression
Edinger, A. L. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330225 · Cited by 23
Brandsch, M., Leibach, F. H., Mahesh, V. B., & Ganapathy, V. (1994) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(94)90116-3 · Cited by 20
Kulanthaivel, P., Miyamoto, Y., Mahesh, V. B., Leibach, F. H., & Ganapathy, V. (1991) · Placenta · doi:10.1016/0143-4004(91)90341-c · Cited by 14
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Metadata
- Authors
- Roos, S., Kanai, Y., Prasad, P. D., Powell, T. L., & Jansson, T.
- Affiliations
- University of Gothenburg (SE)
- The University of Osaka (JP)
- University of Cincinnati (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2009-01
- Volume
- 296
- Issue
- 1
- Pages
- C142-C150
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2131629100
- Cited by
- 150
- References
- 69
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 8 · 2012: 16
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR signaling, fetal growth restriction, system L amino acid transporter, system A amino acid transporter, taurine transporter, LAT1, rapamycin, trophoblast, post-translational regulation, placenta
- MeSH terms
- Taurine Transporters, Cell Survival, Cells, Cultured, Female, Humans, Membrane Glycoproteins, Pregnancy, Protein Kinases, Protein Processing, Post-Translational, RNA, Messenger, Time Factors, Trophoblasts, Signal Transduction, Apoptosis, Sirolimus, Protein Transport, Membrane Transport Proteins, Amino Acid Transport Systems, Amino Acid Transport System A, Amino Acid Transport System L, TOR Serine-Threonine Kinases
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