PHOSPHOLIPIDS REACYLATION COULD CONTROL THE CELLULAR SENSITIVITY TO TUMOR NECROSIS FACTOR-ALPHA CYTOTOXICITY

C. Levrat, P. George, C. Rey and P. Louisot
Department of Biochemistry, INSERM 189, Lyon-Sud Medical School, PO Box 12, FR-69921 Oullins, Cedex, France

We have previously reported that Tumor Necrosis Factor-a (TNF-a) induced a stimulation of mitochondrial phospholipase A2 in the the WEHI-164 cell line highly sensitive to its cytotoxic action [1], this perturbation was not detected in the C6 cell line which is completely resistant. So we hypothesize that the action of phospholipase A2 could be reversed by the acyltransferase after activation of a polyunsaturated fatty acid by the acylCoA synthase and ATP and be one of the mechanisms controlling the cellular sensitivity to TNF-a cytotoxicity. Our present data report that the mitochondrial reacylation of phosphatidylcholine as phosphatidylethanolamine was strongly higher in C6 than WEHI-164 cells. TNF-a did not modify the phospholipids reacylation in C6 while in WEHI-164 it was several fold increased. These results suggest that if it 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.

[1]  Levrat, C. and Louisot, P. (1996) Biochem. Biophys. Res. Commun. 221:531-538

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