J. Lipid Res.
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A more recent version of this article appeared on January 1, 2003

Papers In Press, published online ahead of print October 1, 2002
J. Lipid Res., doi:10.1194/jlr.M200312-JLR200
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Submitted on August 7, 2002
Revised on October 25, 2002
Accepted on October 1, 2002

Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of glioma cell proliferation

Kjetil Berge, Karl Johan Tronstad, Pavol Bohov, Lise Madsen, and Rolf Kristian Berge

Department of Clinical Biochemistry, Bergen N-5021

Corresponding Author: mfakb{at}ikb.uib.no

Tetradecylthioacetic acid (TTA), which can not be â-oxidized, exert growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatty acid palmitic acid (PA), in the presence of L-carnitine and the carnitine palmitoyltransferase inhibitors etomoxir and aminocarnitine. L-carnitine partly abolished the PA-mediated growth reduction of glioma cells, whereas etomoxir and aminocarnitine enhanced the antiproliferative effect of PA. The production of acid-soluble products increased and the incorporation of PA into glycerolipids decreased after L-carnitine supplementation. L-carnitine was found to enhance the antiproliferative effect of TTA, but did not affect the incorporation of TTA into glycerolipids, as well as ceramide. Neither PDMP, sphingosine 1-phosphated, desipramine, fumonisin B1 nor L-cycloserine was able to rescue the glioma cells from PA and TTA-induced growth inhibition, suggesting that increased ceramide production is not important in the growth reduction. TTA-mediated growth inhibition was accompanied with an increased uptake of PA and increased incorporation of PA into TG. Our data suggest that mitochondrial functions are involved in fatty acid-mediated growth inhibition. Whether there is a causal relationship between TG accumulation and the apoptotic process remains to be determined.


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