Phospholipids reacylation and palmitoylcoa control tumour necrosis factor-alpha sensitivity.
From the hypothesis that in TNF-alpha-resistant cells the activity of mitochondrial phospholipase A2 could be reversed by a lysophospholipid acyltransferase, we report that the mitochondrial reacylation of phosphatidylcholine as phosphatidylethanolamine was considerably higher in C6 (TNF-alpha-resistant) than in WEHI-164 (TNF-alpha-sensitive) cells. TNF-alpha did not modify the phospholipids' reacylation in C6, while in WEHI-164 it was increased several-fold. These results suggest that TNF-alpha is not sufficient to restore the barrier permeability in sensitive cells, but may be enough to explain the absence of permeability change in resistant cells. AcylCoA esters, depending on whether the acyl group is unsaturated or saturated (palmitic acid), could control membrane permeability either by participating in the reacylation of phospholipids or keeping the pore in a closed state. The analysis of the endogenous acylCoA ester pools of both cell lines show that the amount of palmitoylCoA is higher in resistant than sensitive cell lines. TNF-alpha treatment does not change these results.
George
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Department of Biochemistry, INSERM-CNRS 189, Lyon-Sud Medical School, Oullins, cedex, 69921, France. levrat@lyon-sud.univ-lyon1.fr
Ardail
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Rey
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Louisot
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Levrat
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D000107:Acetylation; D000214:Acyl Coenzyme A / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004952:Esters / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019787:Linoleic Acid / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000214:Acyl Coenzyme A; D004952:Esters; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; D010171:Palmitoyl Coenzyme A; D019308:Palmitic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019787:Linoleic Acid