Yano M, Kishida E, Iwasaki M, Kojo S, Masuzawa Y
Department of Life and Health Sciences, Hyogo University of Teacher Education, Yashiro, Hyogo 673-1494, Japan.
J Nutr. 2000 May;130(5):1095-101. doi: 10.1093/jn/130.5.1095.
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.
探讨了多不饱和脂肪酸和维生素E对肿瘤坏死因子（TNF）诱导的人单核细胞U937细胞凋亡的影响，以评估这些营养素在多大程度上可以减轻细胞凋亡。用花生四烯酸对U937细胞进行24小时预孵育不影响TNF诱导的细胞凋亡。仅在无环己酰亚胺（CHI）存在下由TNF诱导细胞凋亡时，二十碳五烯酸略微但显著降低了凋亡细胞的比例。相比之下，用二十二碳六烯酸（DHA）预孵育能极大地（约40%至70%）减轻由TNF或TNF + CHI刺激3小时所诱导的细胞凋亡。细胞凋亡的抑制伴随着DHA在膜磷脂中的富集，这表明DHA可能在掺入磷脂后发挥其抑制活性。维生素E在添加TNF 3小时后也作为细胞凋亡的部分抑制剂发挥作用。这种维生素可以进一步减少经DHA处理的细胞的凋亡，并且当以低频率诱导细胞凋亡时，这种相加作用很明显。用TNF对U937细胞进行更长时间的刺激表明，在添加TNF 9小时后，用DHA或维生素E对细胞进行预孵育对细胞凋亡的抑制作用不显著，但即使在这个时间点，用DHA和维生素E同时进行预孵育也可以降低凋亡细胞的比例。我们的研究结果表明，摄入DHA和维生素E等营养素可能对与各种TNF相关疾病相关的器官功能障碍产生有益影响。
