Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis.
Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002849:Chromatography, Gas; D019610:Cytoprotection / Q000502:physiology; D015777:Eicosanoids / Q000096:biosynthesis; D004789:Enzyme Activation / Q000502:physiology; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000378:metabolism*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000378:metabolism; D022761:Gene Transfer, Horizontal; D006133:Growth Substances / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D006133:Growth Substances; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases