E. Kishida et al., DISTINCTIVE INHIBITORY ACTIVITY OF DOCOSAHEXAENOIC ACID AGAINST SPHINGOSINE-INDUCED APOPTOSIS, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1391(3), 1998, pp. 401-408
The effect of supplementation of docosahexaenoic acid (DHA) on the apo
ptosis of HL60 cells was examined using N-acetyl sphingosine (C-2-cera
mide) and sphingosine as apoptosis-inducing agents. Although C-2-ceram
ide-induced apoptosis was not affected by DHA supplementation, sphingo
sine-induced apoptosis was reduced almost to the background level by p
reincubation with 10 mu M DHA for 24 h. Among the fatty acids, only DH
A appeared to be endowed with the ability to reduce sphingosine-induce
d apoptosis, whereas, other unsaturated fatty acids, such as arachidon
ic acid (AA) and eicosapentaenoic acid (EPA), did not show this activi
ty. Incubation of HL60 with DHA within 6 h did not affect the apoptosi
s, suggesting that DHA probably expressed the inhibitory activity afte
r modulation of the membrane fatty acid composition. DHA also attenuat
ed the apoptosis induced by dimethylsphingosine and H-7, but not by ca
lphostin C, indicating that enrichment of DHA in membranous phospholip
id does not necessarily prevent all of the apoptosis associated with t
he inhibition of protein kinase C. The mechanism of the inhibition aga
inst sphingosine-induced apoptosis by DHA remains to be further explor
ed. However, the inhibition of cytosolic phospholipase A(2)(cPLA(2)) m
ay be involved in the mechanism, because distinctive inhibitory activi
ty of DHA against cPLA(2) has been demonstrated [M. Shikano, Y. Masuza
wa, K. Yazawa, K. Takayama, I. Kudo, K. Inoue, Biochim, Biophys. Acta,
1212, 1994, 211-216], and arachidonyl trifluoromethylketone,a specifi
c inhibitor of cPLA(2), attenuated the apoptosis induced by sphingosin
e. (C) 1998 Elsevier Science B.V.