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Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2

Todesco, L. and Bur, D. and Brooks, H. and Török, M. and Landmann, L. and Stieger, B. and Krähenbühl, S.. (2008) Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2. Cellular and molecular life sciences, Vol. 65, no. 10. pp. 1596-1608.

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Official URL: http://edoc.unibas.ch/dok/A6006021

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Abstract

The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in vivo.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
UniBasel Contributors:Krähenbühl, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Birkhäuser
ISSN:1420-9071
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:25 Apr 2014 08:01
Deposited On:25 Apr 2014 08:01

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