Phospholipase D as a potential target for the antiproliferative effects of polyunsaturated fatty acids in rat thymocytes.
The effects of various saturated and unsaturated fatty acids (FAs) on the proliferative response and phospholipase D (PLD) activity of rat thymocytes were investigated. When added to culture medium as complexes with albumin, all the FAs tested, except stearic acid, inhibited the ConA-induced thymocyte proliferation, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids being the most inhibitory. Apart from 22:6n-3 which slightly increased the percentage of late apoptotic and necrotic thymocytes in the presence of mitogen, none of the FAs induced significant apoptosis or necrosis. A short 2-h preincubation of rat thymocytes in the presence of FA-albumin complexes was sufficient to induce a significant enrichment of cell phospholipids with each FA and to stimulate thymocyte PLD activity. However, 20:5n-3 was inactive despite a large enrichment in phospholipids. Furthermore, the PLD activity of activated thymocytes was negatively correlated to the proliferative response, with the exception of 20:5n-3-supplemented cells. These results support further our current hypothesis that PLD activity conveys antiproliferative signals in lymphoid cells, and suggest that 20:5n-3 inhibits thymocyte proliferation by a particular mechanism unrelated to that of the other FAs.
Benzaria
Amal
A
ALNSERM U585, INSA-Lyon, Physiopathologie des Lipides et Membranes, IMBL, F-69621 Villeurbanne, France.
Meskini
Nadia
N
Dubois
Madeleine
M
Némoz
Georges
G
Lagarde
Michel
M
Prigent
Annie-France
AF
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010739:Phospholipase D