CPT1{alpha} over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

Journal Article · Fri Dec 16 00:00:00 EST 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2005.1· OSTI ID:20793217

Jambor de Sousa, Ulrike L ^[1]; Koss, Michael D ^[1]; Fillies, Marion ^[2]; Gahl, Anja ^[2]; Scheeder, Martin R.L. ^[1]; Cardoso, M Cristina ^[2]; Leonhardt, Heinrich ^[2]; Geary, Nori ^[1]; Langhans, Wolfgang ^[1]; Leonhardt, Monika ^[1]

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1. Institute of Animal Sciences, Swiss Federal Institute of Technology, Zurich (Switzerland)
2. Max Delbrueck Center for Molecular Medicine, Berlin (Germany)

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 1{alpha} (CPT1{alpha}). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1{alpha} 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. CPT1{alpha} over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1{alpha} over-expressing cells in a concentration-dependent manner. Both, PA and CPT1{alpha} over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1{alpha}, 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.

• OSTI ID: 20793217
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 338, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.10.016; PII: S0006-291X(05)02236-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CARNITINE
CELL PROLIFERATION
ENZYMES
HEXADECANOIC ACID
IN VIVO
KIDNEYS
METABOLISM
MITOCHONDRIA
OXIDATION
TRANSLOCATION