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Article

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

Midori Yano^*, Etsu Kishida^*, Maiko Iwasaki^*, Shosuke Kojo and Yasuo Masuzawa^*1

^* Department of Life and Health Sciences, Hyogo University of Teacher Education, Yashiro, Hyogo 673-1494, Japan; and Department of Food Science and Nutrition, Nara Women’s University, Nara 630-8506 Japan

¹To whom correspondence should be addressed.

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 ~ 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.

KEY WORDS: • apoptosis • DHA • tumor necrosis factor • U937 cells • vitamin E