This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Thongsong, B. Articles by Prasad, P. D. Search for Related Content PubMed PubMed Citation Articles by Thongsong, B. Articles by Subramanian, R. K. Articles by Ganapathy, V. Articles by Prasad, P. D. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Pregnancy Social Bookmarking                         What's this?

Inhibition of Amino Acid Transport System A by Interleukin-1ß in Trophoblasts

Radhika K. Subramanian, MBBS

Vadivel Ganapathy, PhD

Departmetns of Biochemistry and Molecular Biology, and Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia

Puttur D. Prasad, PhD

Departmetns of Biochemistry and Molecular Biology, and Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia pprasad{at}mail.mcg.edu

Objective: The current study sought to investigate the influence of interleukin-1ß (IL-1ß) on the function of the amino acid transport system A in trophoblasts.

Methods: BeWo choriocarcinoma cells were exposed to recombinant human IL-1ß in serum-free medium. Cells incubated with serum-free medium in the absence of IL-1ß were used as control. System A activity was determined in control and treated cells by measuring the uptake of -(methylamino)isobutyric acid. The results obtained were confirmed by measuring system. A activity in placental brush border membrane vesicles isolatewd from pregnant rats injected with IL-1ß.

Results: Treatment of BeWe cells with IL-1ß resulted in a time- and dose- dependent inhibition of system A. Treatment with IL-1ß also inhibited the uptake of arginine, and glutamate but had no significant effect on the uptake of leucine, tryptophan, and ascorbate. The inhibition of system A activity by IL-1ß was abolished in the presence of IL-1ß receptor antagonist. The inhibitory effect was associated with a decrease in the maximal velocity of the transport system with no effect on the substrate affinity. Steady-state levels of both SNAT1 and SNAT2 mRNA were reduced by IL-1ß treatment as evidenced by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In rat placental brush border membrane vesicles isolated from IL-1ß-treated pregnant rats, system. A activity was found to be decreased by approximately 40% compared to activity in control membrane vesicles.

Conclusions: IL-1ß decreases SNAT1 and SNAT2 mRNA levels in trophoblasts, which is associated with a decrease in system A-mediated transport activity at the functional level. These findings may have important consequences under both physiologic conditions and pathologic conditions during pregnancy that are associated with elevated levels of IL-1ß.

Key Words: Pregnancy • interleukins • amino acid transporter • regulation • trophoblast

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 7, 495-503 (2005)
DOI: 10.1016/j.jsgi.2005.06.008


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?