Induction of apoptosis by polyunsaturated fatty acids and its relationship to fatty acid inhibition of carnitine palmitoyltransferase I activity in Hep2 cells.
The effects of fatty acids on the induction of apoptosis were studied over a 24 hour period in Hep2 human larynx tumour cells. While oleic and linoleic acids had little effect on the apoptotic index, the polyunsaturated fatty acids alpha-linolenic, gamma-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids all induced apoptosis, beginning at approximately 6 hours after fatty acid exposure. By 24 hours after exposure, the apoptotic index had reached as much as 19% in the presence of docosahexaenoic or alpha-linolenic acid. The correlation between degree of unsaturation of the 18-carbon fatty acids and the apoptotic index was r2 = 0.45, 0.89, 0.84 and 0.98 at 6, 8, 12 and 24 hours, respectively. The correlation between mitochondrial carnitine palmitoyltransferase I (CPT I) activity, 6 hours after exposure, and the apoptotic index was r2 = 0.842 and 0.798 at 12 and 24 hours, respectively. The inhibition of CPT I and subsequent fatty acid oxidation by polyunsaturated fatty acids leads to a significant increase in apoptosis, suggesting that CPT I may be involved in the processes of programmed cell death in Hep2 human tumour cells.
Departamento de Histologia e Embriologia, Universidade de São Paulo, Brasil. Alison@usp.br
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Colquhoun
D017209:Apoptosis; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D002334:Carnitine O-Palmitoyltransferase