L-Carnitine Regulates mRNA Expression Levels of the Carnitine Acyltransferases – CPT1A, CPT2, and CRAT

In order to analyze the biological influence of carnitine on the transcriptional regulation of mitochondrial carnitine acetyltransferase (CRAT) and carnitine palmitoyltransferases (CPT1A and CPT2) in conditions simulating carnitine deficiency in vivo, we cultured mouse (rat) fibroblasts and human liver cells with dialysed serum (carnitine deficient). The transcript levels of all three genes were 2-3-fold down-regulated after cultivation with dialysed serum compared to mRNA values with non-dialysed serum. The down-regulation of transcripts was fully reverted by carnitine supplementation. CPT1A and CRAT mRNA levels reached peak values 8 and 24 h after carnitine addition, respectively, and declined thereafter. The mRNA levels of CPT2 were induced more than five-fold after 48 h. Carnitine-induced accumulation of the carnitine acyltransferases was not caused by the alteration of mRNAs’ stability by carnitine. The levels of CPT1A and CRAT steady state transcripts decreased also during cultivation in fetal calf serum, having a lower carnitine content than calf serum. During the cell cycle, carnitine acyltransferases seem to be regulated in a similar manner. On the other hand, the patterns of regulation after serum stimulus are different and appeared to be dependent on the presence or absence of carnitine in non-dialysed or dialysed serum, respectively.