Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9)

Lüscher, Benjamin; Clemençon, Benjamin; Marini, Camilla; Huang, Xiao; Sager, Ruth; Jeanneret, Céline; Reymond, Jean-Louis; Albrecht, Christiane; Hediger, Matthias; Surbek, Daniel; Baumann, Marc Ulrich (January 2014). Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). Reproductive sciences, 21(3), 303A-303A. Sage

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Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). INTRODUCTION: Pre-eclampsia, a pregnancy-specific disease, contributes substantially to perinatal morbidity and mortality of both the mother and her child. Pre-eclampsia is often associated with high maternal urate serum levels, which in turn has been shown to play a role in the pathogenesis of this disease. The aim of this study was to investigate the glucose transporter GLUT9-mediated placental uric acid transport system. METHODS: In this study western blot, immunofluorescence techniques as well as a transepithelial transport (Transwell) model were used to assess GLUT9 protein expression and, respectively, uric acid transport activity. Electrophysiological techniques and transmission electron microscopy (TEM) were used to characterize the properties and the structure of GLUT9. RESULTS: Uric acid is transported across a BeWo choriocarcinoma cell monolayer with 530 pmol/min. We could successfully overexpress and for the first time purify the GLUT9b isoform using the Xenopus laevis oocytes expression system. Chloride seems to modulate the urate transport system. TEM revealed that GLUT9b isoform is present as monomer and dimmer in the Xenopus laevis overexpression model. A class average of all the particles allowed us to develop a first model of human GLUT9b structure, which was derived from the published crystal structure of the bacterial homologue of GLUT1-4. CONCLUSIONS: In vitro the “materno-fetal” transport of uric acid is slow indicating that in vivo the fetus might be protected from short-term fluctuations of maternal urate serum levels. The low-resolution structure obtained from TEM validates the proposed homology model regarding the structure of human GLUT9b. In ongoing studies this model is used to perform virtual screening to identify novel modulators of the urate transport system enabling the development of novel therapies in pregnancy complications.

Item Type:

Conference or Workshop Item (Abstract)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Lüscher, Benjamin; Clemençon, Benjamin; Marini, Camilla; Huang, Xiao; Sager, Ruth; Reymond, Jean-Louis; Albrecht, Christiane; Hediger, Matthias; Surbek, Daniel and Baumann, Marc Ulrich

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
500 Science > 540 Chemistry

ISSN:

1933-7191

Publisher:

Sage

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

02 Apr 2015 12:00

Last Modified:

02 Sep 2015 10:23

BORIS DOI:

10.7892/boris.67507

URI:

https://boris.unibe.ch/id/eprint/67507

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