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Functional characterization of tyrosine and tryptophan transport in fibroblasts from healthy controls, patients with schizophrenia and bipolar disorder
Örebro University, School of Health and Medical Sciences. (Neuropsychiatric Research Laboratory)
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 [en]
Fibroblasts, Tyrosine, Tryptophan, LAT1, Schizophrenia, Bipolar disorder
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-6393ISBN: 978-91-7668-668-3 (print)OAI: oai:DiVA.org:oru-6393DiVA: diva2:213655
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
List of papers
1. Aberrant amino acid transport in fibroblasts from patients with bipolar disorder
Open this publication in new window or tab >>Aberrant amino acid transport in fibroblasts from patients with bipolar disorder
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2009 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 457, no 1, 49-52 p.Article in journal (Refereed) Published
Abstract [en]

Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n = 10) and healthy controls (n = 10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (Vmax) and affinity constant (Km) were determined. A significantly lower Vmax for tyrosine (p = 0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in Km for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low Vmax) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

Place, publisher, year, edition, pages
Elsevier, 2009
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-6392 (URN)10.1016/j.neulet.2009.03.095 (DOI)000266360300012 ()19429160 (PubMedID)2-s2.0-67349103112 (Scopus ID)
Available from: 2009-04-27 Created: 2009-04-27 Last updated: 2017-02-23Bibliographically approved
2. Functional characterization of tyrosine transport in fibroblast cells from healthy controls
Open this publication in new window or tab >>Functional characterization of tyrosine transport in fibroblast cells from healthy controls
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2008 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 434, no 1, 56-60 p.Article in journal (Refereed) Published
Abstract [en]

Human fibroblast cells are an advantageous model to study the transport of amino acids across cell membranes, since one can control the environmental factors. A major problem in all earlier studies is the lack of precise and detailed knowledge regarding the expression and functionality of tyrosine transporters in human fibroblasts. This motivated us to perform a systematic functional characterization of the tyrosine transport in fibroblast cells with respect to the isoforms of system-L (LAT1, LAT2, LAT3, LAT4), which is the major transporter of tyrosine. Ten (n = 10) fibroblast cell lines from healthy volunteers were included in the study. Uptake of L-[U-14C] tyrosine in fibroblasts was measured using the cluster tray method in the presence and absence of excess concentrations of various combinations of inhibitors. This study demonstrated that LAT1 is involved in 90% of total uptake of tyrosine and also around 51% of alanine. Not more than 10% can be accounted for by LAT2, LAT3 and LAT4 isoforms. LAT2 seems to be functionally weak in uptake of tyrosine while LAT3 and LAT4 contributed around 7%. 10% could be contributed by system-A (ATA2 isoform). Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine transport through the LAT1 isoform has a higher affinity compared to system-L. In conclusion, the LAT1 isoform is the major transporter of tyrosine in human fibroblast cells. Competition between tyrosine and alanine for transport is shown to exist, probably between LAT1 and LAT2 isoforms. This study established fibroblast cells as a suitable experimental model for studying amino acid transport defects in humans.

National Category
Medical and Health Sciences Neurology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-3017 (URN)10.1016/j.neulet.2008.01.028 (DOI)
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2016-12-12Bibliographically approved
3. Tyrosine transport through LAT1 transport system in fibroblasts of schizophrenic patients and healthy controls
Open this publication in new window or tab >>Tyrosine transport through LAT1 transport system in fibroblasts of schizophrenic patients and healthy controls
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(English)Manuscript (Other academic)
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-3018 (URN)
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2016-12-12Bibliographically approved
4. Functional characterization of tryptophan transport in human fibroblast cells
Open this publication in new window or tab >>Functional characterization of tryptophan transport in human fibroblast cells
(English)Manuscript (Other (popular science, discussion, etc.))
Keyword
Fibroblasts, tryptophan, serotonin, amino acid transporters
National Category
Neurosciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-6391 (URN)
Available from: 2009-04-27 Created: 2009-04-27 Last updated: 2016-12-12Bibliographically approved

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