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Tyrosine transport through LAT1 transport system in fibroblasts of schizophrenic patients and healthy controls
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
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(English)Manuscript (Other academic)
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-3018OAI: oai:DiVA.org:oru-3018DiVA: diva2:136355
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2016-12-12Bibliographically approved
In thesis
1. Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
Open this publication in new window or tab >>Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
2008 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

ABSTRACT

Cultured human fibroblasts offer an advantageous system to investigate the amino acid transport properties without confounding the affects of disease state and its treatment in many systemic psychiatric disorders. In previous studies, fibroblast cells have been used to investigate the tyrosine transport across plasma membranes in patients with schizophrenia and autism with out characterizing the particular amino acid transporters.

The importance of the major tyrosine transporters (system-L and system-A) was investigated in this study. Systemic functional characterization of tyrosine transport in fibroblasts from healthy controls and patients with schizophrenia, with respect to the system-L isoforms (LAT1, LAT2, LAT3, and LAT4) was performed.

Ten (n=10) fibroblast cell lines from healthy controls and ten (n=10) from patients with schizophrenia were included in this study. Transport and uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in the absence and presence of different specific inhibitors. The maximal transport capacity, Vmax and the affinity constant of the tyrosine-binding site, Km, of LAT1 isoform were determined.

The results of this study showed that tyrosine transport in fibroblasts is facilitated mainly by the system-L and LAT1 isoform is involved in 90% of total tyrosine uptake. LAT2 isoform seems to be functionally weak in uptake of tyrosine, as not more than 3% could be contributed by it. LAT3 and LAT4 contributed around 7%. System-A (ATA2 isoform) contributed around 10%. Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine uptake and kinetics did not differ between patients and controls at the LAT1 isoform. Moreover, the affinity of LAT1 isoform for tyrosine was higher when compared to system-L. LAT1 is also involved in around 51% of uptake of alanine.

In conclusion, the present thesis, confirms the presence of system-L with its isoform LAT1 as a main transporter of tyrosine in human fibroblast cells. The competition between tyrosine and alanine to get transported is shown to probably exist mainly at LAT1 isoform. Aberrant tyrosine transport observed in previous studies in patients with schizophrenia is probably not linked to the LAT1 isoform. This study gave further importance and established fibroblast cells as a suitable experimental model for studying amino acid transport properties in humans.

Key words: Fibroblasts, Tyrosine and alanine transport, System-L, LAT1, LAT2, LAT3, LAT4, Schizophrenia, Precursor of Dopamine.

Place, publisher, year, edition, pages
Örebro: Örebro universitetsbibliotek, 2008. 65 p.
Keyword
Fibroblasts, Schizophrenia, Precursor of Dopamine, Biological Transport, Active/cellphysiology, Tyrosine and alanine transport, System-L, LAT1, LAT2, LAT3, LAT4
National Category
Medical and Health Sciences Clinical Medicine Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:oru:diva-2520 (URN)1653-1280 (ISBN)
Presentation
(English)
Supervisors
Available from: 2009-02-24 Created: 2008-10-21 Last updated: 2010-02-03Bibliographically approved
2. Functional characterization of tyrosine and tryptophan transport in fibroblasts from healthy controls, patients with schizophrenia and bipolar disorder
Open this publication in new window or tab >>Functional characterization of tyrosine and tryptophan transport in fibroblasts from healthy controls, patients with schizophrenia and bipolar disorder
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. 65 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 30
Keyword
Fibroblasts, Tyrosine, Tryptophan, LAT1, Schizophrenia, Bipolar disorder
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-6393 (URN)978-91-7668-668-3 (ISBN)
Public defence
2009-05-29, Lokal HSM (Hörsal Musikhögskolan), Musikhögskolan, Örebro University, Örebro, 13:15 (English)
Opponent
Supervisors
Available from: 2009-04-28 Created: 2009-04-27 Last updated: 2011-05-02Bibliographically approved

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