Docosahexaenoic Acid and Vitamin E Can Reduce Human Monocytic U937 Cell Apoptosis Induced by Tumor Necrosis Factor

Abstract

The effects of polyunsaturated fatty acids and vitamin E on tumor necrosis factor (TNF)-induced apoptosis of human monocytic U937 cells was explored to assess to what extent these nutrients could attenuate apoptosis. Preincubation of U937 cells with arachidonic acid for 24 h did not affect TNF-induced apoptosis. Eicosapentaenoic acid slightly but significantly reduced the proportion of apoptotic cells only when apoptosis was induced by TNF without cycloheximide (CHI). In contrast, preincubation with docosahexaenoic acid (DHA) greatly (40 approximately 70%) attenuated apoptosis induced by stimulation with either TNF or TNF + CHI for 3 h. The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA probably exerted its inhibitory activity after being incorporated into the phospholipids. Vitamin E also played a role as a partial inhibitor of apoptosis 3 h after TNF addition. This vitamin could further reduce the apoptosis of DHA-treated cells, and such an additive effect was obvious when apoptosis was induced at a low frequency. Longer-range stimulation of U937 cells with TNF showed that inhibition of apoptosis by preincubating cells with either DHA or vitamin E was not significant 9 h after TNF addition, but that preincubation with both DHA and vitamin E could reduce the proportion of apoptotic cells even at this time point. Our findings suggested that ingestion of nutrients such as DHA and vitamin E might exert beneficial effects on organ dysfunction associated with various TNF-related diseases.

Mechanisms of action of docosahexaenoic acid in the nervous system

“…Considering the fact that PS is the major negatively charged phospholipid class in many mammalian cell membranes and many of the signaling proteins such as protein kinases are influenced by PS (119-121), this alteration of PS content may have significant implications for cellular function. In contrast to the well-documented apoptotic effect of DHA (122)(123)(124)(125)(126)(127), only a few studies have indicated an antiapoptotic function for this fatty acid (128)(129)(130)(131). In each case, an antiapoptotic effect was observed only after preincubation with DHA before the induction of apoptosis.…”

“…Because DHA is prone to oxidation during the incubation period and much of the apoptotic effect is mediated through oxidative stress (126,127), it is difficult to successfully enrich cultured cells with DHA without accompanying lipid peroxidation. Therefore, to observe the antiapoptotic effect of DHA, it is crucial that an antioxidant such as vitamin E be added along with DHA to the culture medium (130,131).…”

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

“…Still other studies have shown that linoleic acid (n-6) decreases the activity of IL-2 [129], and increases IL-1 production and tissue response to cytokines, while n-3 generally decreases IL-1 production and activity [44]. Despite some disagreement among studies, it seems that n-3 fatty acids (alpha-linolenic acid, DHA, EPA) decrease the production and activity of the pro-inflammatory cytokines (IL-1, IL-6, TNF alpha ) [13,20,52,124] and that n-6 family has the opposite effect [19,44,54]. The ability of n-3 PUFA to reduce pro-inflammatory cytokines and prostaglandin [21] lead to the proposal for the use of fish oil to relieve pain.…”

Vitamin E Regulation of Mitochondrial Superoxide Generation

“…These data suggest that antioxidant administration decreased the radiation-induced apoptosis and delayed internucleosomal fragmentation of DNA and that radiation-induced alteration of gene expression is, at least in part, determined by ROS. Similarly, vitamin E has been shown to prevent apoptosis in cortical neurons during hypoxia and oxygen reperfusion [96], and reduce human monocytic U937 apoptosis induced by TNF [97].…”