PMID- 16246309 OWN - NLM STAT- MEDLINE DCOM- 20060112 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 338 IP - 2 DP - 2005 Dec 16 TI - CPT1alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells. PG - 757-61 AB - To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1alpha (CPT1alpha). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1alpha transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1alpha over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1alpha over-expressing cells in a concentration-dependent manner. Both, PA and CPT1alpha over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1alpha, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo. FAU - Jambor de Sousa, Ulrike L AU - Jambor de Sousa UL AD - Institute of Animal Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland. FAU - Koss, Michael D AU - Koss MD FAU - Fillies, Marion AU - Fillies M FAU - Gahl, Anja AU - Gahl A FAU - Scheeder, Martin R L AU - Scheeder MR FAU - Cardoso, M Cristina AU - Cardoso MC FAU - Leonhardt, Heinrich AU - Leonhardt H FAU - Geary, Nori AU - Geary N FAU - Langhans, Wolfgang AU - Langhans W FAU - Leonhardt, Monika AU - Leonhardt M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051013 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Fatty Acids) RN - 0 (Recombinant Proteins) RN - 2V16EO95H1 (Palmitic Acid) RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) SB - IM MH - Carnitine O-Palmitoyltransferase/genetics/*metabolism MH - Cell Line MH - Cell Survival/physiology MH - Fatty Acids/*metabolism MH - Gene Expression Regulation/physiology MH - Humans MH - Kidney/*cytology/*metabolism MH - Lipid Peroxidation/physiology MH - Oxidation-Reduction MH - Palmitic Acid/*metabolism MH - Recombinant Proteins/metabolism EDAT- 2005/10/26 09:00 MHDA- 2006/01/13 09:00 CRDT- 2005/10/26 09:00 PHST- 2005/09/29 00:00 [received] PHST- 2005/10/03 00:00 [accepted] PHST- 2005/10/26 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/10/26 09:00 [entrez] AID - S0006-291X(05)02236-9 [pii] AID - 10.1016/j.bbrc.2005.10.016 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2005 Dec 16;338(2):757-61. doi: 10.1016/j.bbrc.2005.10.016. Epub 2005 Oct 13.