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

被引：19

作者：

Todesco, L. ^{[1
,2
]}

Bur, D. ^{[3
]}

Brooks, H. ^{[1
,2
]}

Toeroek, M. ^{[1
,2
]}

Landmann, L. ^{[4
]}

Stieger, B. ^{[5
]}

Kraehenbuehl, S. ^{[1
,2
]}

机构：

[1] Univ Basel Hosp, Div Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland

[2] Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland

[3] Actelion Ltd, Allschwil, Switzerland

[4] Univ Basel, Inst Anat & Embryol, Basel, Switzerland

[5] Univ Zurich Hosp, Div Clin Pharmacol & Toxicol, CH-8091 Zurich, Switzerland

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2008年 / 65卷 / 10期

关键词：

hOCTN2; secondary carnitine deficiency; drug-carnitine interactions; stable transfection; acylcarnitines; verapamil;

D O I：

10.1007/s00018-008-8065-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1596 / 1608

页数：13

共 40 条

[1] Applications of the Cambridge Structural Database in organic chemistry and crystal chemistry [J].