Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts
Abstract
We tested the hypothesis that hypoxia diminishes the expression and transport of neutral amino acids by system A in full-term human trophoblasts. Cytotrophoblasts from normal human placentas were cultured in standard conditions of 20% O 2 or in 1% and 3% O 2 for 24 h before assay. Neutral amino acid transport for systems A, ASC, and L was assayed at 24 and 72 h by the cluster-tray technique. Hypoxia during the initial 24 h of culture reduced system A transport by 82% in 1% O 2 and by 37% in 3% O 2 ( P < 0.01) compared with standard conditions. Hypoxia during the latter 24 h of the 72 h in culture reduced system A transport by 55% in 1% O 2 and by 20% in 3% O 2 ( P < 0.05) compared with standard conditions at 72 h. Hypoxia (1% O 2) also reduced total amino acid transport by 40% in the more differentiated syncytiotrophoblasts present at 72 h. Northern analysis of trophoblasts in standard conditions showed that subtypes of human amino acid transporter A (hATA1 and hATA2) were each expressed in cytotrophoblasts and syncytiotrophoblasts. Hypoxia decreased expression of hATA1 and hATA2 in both trophoblast phenotypes. We conclude that hypoxia downregulates system A transporter expression and activity in cultured human trophoblasts.
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In human placentas in vitro, exposure to acute episodes of hypoxia reduces expression and/or activity of accumulative System A amino acid transporters but increases activity of System L amino acid transport.
“In human placentas in vitro, exposure to acute episodes of hypoxia reduces expression and/or activity of accumulative System A amino acid transporters but increases activity of System L amino acid transport (313, 412, 547).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [412]
Cites
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 · see citing works
Intrauterine growth restriction
Resnik, R. (2002) · Obstetrics & Gynecology · doi:10.1016/s0029-7844(01)01780-x · Cited by 1,022 · see citing works
Semenza, G. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00518-9 · Cited by 935 · see citing works
Oxygen and placental villous development: Origins of fetal hypoxia
Kingdom, J. C., & Kaufmann, P. (1997) · Placenta · doi:10.1016/s0143-4004(97)90000-x · Cited by 581 · see citing works
Simple and rapid fluorimetric method for DNA microassay
Kapuściński, J., & Skoczylas, B. (1977) · Analytical Biochemistry · doi:10.1016/0003-2697(77)90533-4 · Cited by 488 · see citing works
Prenatal asphyxia, hyperlacticaemia, hypoglycaemia, and erythroblastosis in growth retarded fetuses.
Soothill, P. W., Nicolaides, K. H., & Campbell, S. (1987) · BMJ · doi:10.1136/bmj.294.6579.1051 · Cited by 371 · see citing works
Diagnostic Value of Blood Sampling in Fetuses with Growth Retardation
Pardi, G., Cetin, I., Marconi, A. M., Lanfranchi, A., Bozzetti, P., Farrazzi, E., Buscaglia, M., & Battaglia, F. C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199303113281004 · Cited by 345 · see citing works
Morrish, D. W., Bhardwaj, D., Dabbagh, L., et al. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-65-6-1282 · Cited by 332 · see citing works
Jansson, T., Wennergren, M., & Illsley, N. P. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.6.8263141 · Cited by 320 · see citing works
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 · see citing works
SOOTHILL, P. W., Nicolaides, K. H., Rodeck, C. H., & Campbell, S. C. (1986) · Fetal Diagnosis and Therapy · doi:10.1159/000262264 · Cited by 265 · see citing works
Cetin, 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 · see citing works
The cluster-tray method for rapid measurement of solute fluxes in adherent cultured cells
Gazzola, G. C., Dall’Asta, V., Franchi‐Gazzola, R., et al. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90019-1 · Cited by 259 · see citing works
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 · see citing works
Amino Acid Transporters in the Human Placenta
Jansson, T. (2001) · Pediatric Research · doi:10.1203/00006450-200102000-00003 · Cited by 245 · see citing works
SOOTHILL, P. W., Nicolaides, K. H., Rodeck, C. H., & Campbell, S. C. (1988) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198843010-00005 · Cited by 227 · see citing works
Levy, R., Smith, S. D., Chandler, K., Sadovsky, Y., & Nelson, D. M. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.278.5.c982 · Cited by 211 · see citing works
Self-citationPaolini, C. L., Marconi, A. M., Ronzoni, S., Noio, M. D., Fennessey, P. V., Pardi, G., & Battaglia, F. C. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.11.8036 · Cited by 210 · see citing works
An Introduction to Fetal Physiology
Battaglia, F. C., & Meschia, G. (1986) · Medical Entomology and Zoology · Cited by 202 · see citing works
Schaiff, W. T., Carlson, M. G., Smith, S. D., Levy, R., Nelson, D. M., & Sadovsky, Y. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6885 · Cited by 189 · see citing works
Self-citationDouglas, G. C., & King, B. F. (1990) · Journal of Cell Science · doi:10.1242/jcs.96.1.131 · Cited by 178 · see citing works
Cetin, I., Marconi, A. M., Bozzetti, P., Sereni, L. P., Corbetta, C., Pardi, G., & Battaglia, F. C. (1988) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(88)90792-2 · Cited by 177 · see citing works
Cetin, I., Ronzoni, S., Marconi, A. M., et al. (1996) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(96)70609-9 · Cited by 175 · see citing works
Placental Transport and Metabolism of Amino Acids
Battaglia, F. C., & Regnault, T. R. H. (2001) · Placenta · doi:10.1053/plac.2000.0612 · Cited by 166 · see citing works
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 · see citing works
Hatanaka, T., Huang, W. Y., Wang, H., et al. (2000) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(00)00252-2 · Cited by 155 · see citing works
Tissue concentrations of free amino acids in term human placentas
Philipps, A. F., Holzman, I. R., Teng, C. C., & Battaglia, F. C. (1978) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)33136-2 · Cited by 155 · see citing works
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 · see citing works
Nelson, D. M., Johnson, R. D., Smith, S. D., Anteby, E. Y., & Sadovsky, Y. (1999) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(99)70661-7 · Cited by 131 · see citing works
Self-citationNeutral amino acid transport systems of microvillous membrane of human placenta
Johnson, L. W., & Smith, C. (1988) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1988.254.6.c773 · Cited by 130 · see citing works
Self-citationNutrient Transport Pathways Across the Epithelium of the Placenta
Smith, C., Moe, A. J., & Ganapathy, V. (1992) · Annual Review of Nutrition · doi:10.1146/annurev.nu.12.070192.001151 · Cited by 121 · see citing works
Self-citationPlacental amino acid transport
Moe, A. J. (1995) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1995.268.6.c1321 · Cited by 119 · see citing works
Amino Acid Interconversions in the Fetal-Placental Unit: The Animal Model and Human Studies In Vivo
Cetin, I. (2001) · Pediatric Research · doi:10.1203/00006450-200102000-00004 · Cited by 112 · see citing works
Alanine transport systems in isolated basal plasma membrane of human placenta
Hoeltzli, S. D., & Smith, C. (1989) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1989.256.3.c630 · Cited by 112 · see citing works
Self-citationWang, H., Huang, W. Y., Sugawara, M., Devoe, L. D., Leibach, F. H., Prasad, P. D., & Ganapathy, V. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3061 · Cited by 108 · see citing works
Self-citationIn Vivo Placental Transport of Glycine and Leucine in Human Pregnancies
Cetin, I., Marconi, A. M., Baggiani, A., et al. (1995) · Pediatric Research · doi:10.1203/00006450-199505000-00002 · Cited by 71 · see citing works
ASC system activity is altered by development of cell polarity in trophoblast from human placenta
Furesz, T. C., Smith, C., & Moe, A. J. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.1.c212 · Cited by 62 · see citing works
Self-citationFunctional characterization of l-alanine transport in a placental choriocarcinoma cell line (BeWo)
Moe, A. J., Furesz, T. C., & Smith, C. H. (1994) · Placenta · doi:10.1016/s0143-4004(05)80182-1 · Cited by 35 · see citing works
Self-citationRegulation of neutral amino acid transport in hepatocytes isolated from adrenalectomized rats
Kilberg, M. S., Vida, T. A., & Barber, E. F. (1983) · Journal of Cellular Physiology · doi:10.1002/jcp.1041140108 · Cited by 32 · see citing works
Dicke, J. M., & Verges, D. K. (1994) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767059409017364 · Cited by 17 · see citing works
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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 · see citing works
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- Authors
- Nelson, D. M., Smith, S. D., Furesz, T. C., Sadovsky, Y., Ganapathy, V., Parvin, C. A., & Smith, C. H.
- Affiliations
- Department of Obstetrics and Gynecology,
- St. Louis Children's Hospital (US)
- Augusta University (US)
- Washington University in St. Louis (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2003-02-01
- Volume
- 284
- Issue
- 2
- Pages
- C310-C315
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2331656809
- Cited by
- 112
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 8 · 2012: 10
- FWCI
- 11.02
- 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 › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- hypoxia, system A amino acid transporter, human trophoblast, cytotrophoblast, syncytiotrophoblast, neutral amino acid transport, transporter gene expression, placenta, oxygen deprivation
- MeSH terms
- Hypoxia, Cells, Cultured, Female, Fetal Hypoxia, Fetal Growth Retardation, Humans, Placenta Diseases, Pregnancy, Trophoblasts, Down-Regulation, Amino Acid Transport System A
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