Cisplatin-induced downregulation of OCTN2 affects carnitine wasting.

ABSTRACT:

Purpose

Carnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function.

Experimental design

Excretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration. The transport of carnitine was assessed in cells that were transfected with OCT1 or OCT2. The effect of cisplatin treatment on gene expression was analyzed using a mouse GeneChip array and validated using quantitative reverse transcriptase-PCR.

Results

In wild-type mice, urinary carnitine excretion at baseline was ∼3-fold higher than

SUBMITTER: Lancaster CS 

PROVIDER: S-EPMC3531239 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature