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

Cellular and Molecular Life Sciences : CMLS
L TodescoS Krähenbühl

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.

Citations

Sep 9, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Manuel HaschkeStephan Krähenbühl
Mar 6, 2012·Molecular Cancer Therapeutics·Chaoxin HuAlex Sparreboom
Feb 10, 2010·Neurochemical Research·Elzbieta JanuszewiczKatarzyna A Nałecz
Jun 23, 2009·Chemico-biological Interactions·Liliane TodescoStephan Krähenbühl
Dec 2, 2008·Chemico-biological Interactions·Lorena PochiniCesare Indiveri
Jun 19, 2013·Journal of Biomolecular Screening·Lorena PochiniCesare Indiveri
Mar 17, 2017·American Journal of Physiology. Cell Physiology·Andy ShawD Lee Hamilton
Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Barbara Juraszek, Katarzyna A Nałęcz
Jun 30, 2012·Therapeutic Drug Monitoring·Réjane MorandStephan Krähenbühl
Jul 13, 2020·Journal of Neurochemistry·Barbara JuraszekKatarzyna A Nałęcz
Oct 31, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sook Wah YeeKathleen M Giacomini
Jul 18, 2018·Journal of Agricultural and Food Chemistry·Luigi ServilloMaria Luisa Balestrieri

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