Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells
Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells
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DOI：
10.3892/mmr.2019.9940
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Hisatomi, Hisashi
中科院分区：
文献类型：
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作者：
Iuchi, Katsuya;Ema, Mika;Hisatomi, Hisashi
多不饱和脂肪酸通过非酶促或酶促反应被氧化。氧化产物具有多功能性。在这项研究中，我们研究了氧化脂肪酸如何抑制培养细胞中的细胞增殖。我们使用多不饱和和饱和脂肪酸、二十二碳六烯酸 (DHA; 22:6)、二十碳五烯酸 (EPA; 20:5)、亚油酸 (LA; 18:2) 和棕榈酸 (16:0)。氧化脂肪酸是通过脂肪酸在气体混合物（20% O-2 和 80% N-2）存在下自动氧化 2 天而产生的。我们发现，在 THP-1（人单核细胞白血病细胞系）和 DLD-1（人结直肠癌细胞系）细胞中，氧化多不饱和脂肪酸（OxDHA、OxEPA 和 OxLA）比未氧化脂肪酸（分别为 DHA、EPA 和 LA）更有效地抑制细胞增殖。特别是，OxDHA 显着抑制细胞增殖。 DHA是脂肪酸中双键数量最多、最容易被氧化的。 OxDHA 具有数量最多的高活性氧化产物。因此，脂肪酸的氧化水平与抗增殖活性相关。此外，Caspase-3/7 在用 OxDHA 处理的细胞中被激活，但在用 DHA 处理的细胞中则没有。泛半胱天冬酶抑制剂 (zVAD-fmk) 减少了 OxDHA 诱导的细胞死亡。这些结果表明，多不饱和脂肪酸的氧化产物诱导培养细胞凋亡。总的来说，细胞存活和细胞死亡之间的转换可以通过多不饱和脂肪酸氧化产物的活性和/或数量来调节。
Polyunsaturated fatty acids are oxidized by non-enzymatic or enzymatic reactions. The oxidized products are multifunctional. In this study, we investigated how oxidized fatty acids inhibit cell proliferation in cultured cells. We used polyunsaturated and saturated fatty acids, docosahexaenoic acid (DHA; 22:6), eicosapentaenoic acid (EPA; 20:5), linoleic acid (LA; 18:2), and palmitic acid (16:0). Oxidized fatty acids were produced by autoxidation of fatty acids for 2 days in the presence of a gas mixture (20% O-2 and 80% N-2). We found that oxidized polyunsaturated fatty acids (OxDHA, OxEPA and OxLA) inhibited cell proliferation much more effectively compared with un-oxidized fatty acids (DHA, EPA and LA, respectively) in THP-1 (a human monocytic leukemia cell line) and DLD-1 (a human colorectal cancer cell line) cells. In particular, OxDHA markedly inhibited cell proliferation. DHA has the largest number of double bonds and is most susceptible to oxidation among the fatty acids. OxDHA has the largest number of highly active oxidized products. Therefore, the oxidative levels of fatty acids are associated with the anti-proliferative activity. Moreover, caspase-3/7 was activated in the cells treated with OxDHA, but not in those treated with DHA. A pan-caspase inhibitor (zVAD-fmk) reduced the cell death induced by OxDHA. These results indicated that oxidized products from polyunsaturated fatty acids induced apoptosis in cultured cells. Collectively, the switch between cell survival and cell death may be regulated by the activity and/or number of oxidized products from polyunsaturated fatty acids.