oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
Örebro University, School of Health and Medical Sciences.
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 [en]
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: urn:nbn:se:oru:diva-2520ISBN: 1653-1280 OAI: oai:DiVA.org:oru-2520DiVA: diva2:136356
Presentation
(English)
Supervisors
Available from: 2009-02-24 Created: 2008-10-21 Last updated: 2010-02-03Bibliographically approved
List of papers
1. 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
Show others...
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
2. 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
Show others...
(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

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Vumma, Ravi
By organisation
School of Health and Medical Sciences
Medical and Health SciencesClinical MedicineNeurology

Search outside of DiVA

GoogleGoogle Scholar

Total: 123 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf