Essential fatty acids, lipid peroxidation and apoptosis
Essential fatty acids, lipid peroxidation and apoptosis
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DOI：
10.1054/plef.1999.0085
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发表时间：
1999-09-01
影响因子：
3
通讯作者：
Das, UN
中科院分区：
文献类型：
--
作者：
Das, UN
已知必需脂肪酸（EFAs）及其代谢产物，特别是γ -亚麻酸、花生四烯酸、二十碳五烯酸和二十碳六烯酸可诱导肿瘤细胞凋亡。但这些脂肪酸诱导细胞凋亡的确切机制尚不清楚。最近的研究表明，这些脂肪酸能够在细胞谷胱甘肽耗竭和肉毒碱棕榈酰转移酶I （CPTI）活性抑制后诱导细胞色素P450过度表达的细胞凋亡。另一方面，BCL-2阻止这些长链脂肪酸诱导的细胞凋亡，其中n-3脂肪酸抑制ras表达，从而抑制显性肿瘤的发展。BCL-2磷酸化抑制其干扰细胞凋亡的能力，增强脂质过氧化导致细胞凋亡的发生。用长链脂肪酸处理的肿瘤细胞显示出脂质过氧化过程增加，抗氧化剂消耗和蛋白质磷酸化。基于这些结果，我们认为长链脂肪酸通过增强脂质过氧化作用诱导细胞凋亡，抑制BCL-2的表达可能是通过磷酸化和增强P450活性来实现的。因此，这些长链脂肪酸实际上可能在基因/癌基因表达水平上对肿瘤细胞产生细胞毒性作用。(C) 1999哈考特出版社有限公司
Essential fatty acids (EFAs) and their metabolites, especially gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid and decosahexaenoic acid are known to induce apoptotic death of tumour cells. But the exact mechanism by which these fatty acids are able to induce apoptosis is not clear. Recent studies suggest that these fatty acids are able to induce apoptosis in cells over expressing cytochrome P450 following depletion of cellular glutathione and inhibition of carnitine palmitoyl transferase I (CPTI) activity. On the other hand, BCL-2 prevented apoptosis induced by these long-chain fatty acids, where as n-3 fatty acids suppressed ras expression leading to suppression of development of overt neoplasia. Phosphorylation of BCL-2 inhibits its ability to interfere with apoptosis and enhances lipid peroxidation leading to the occurrence of apoptosis. Tumour cells treated with long-chain fatty acids show increase in lipid peroxidation process, depletion of antitoxidants and phosphorylation of proteins. Based on these results, it is suggested that long-chain fatty acids induce apoptosis by enhancing lipid peroxidation, suppressing BCL-2 expression possibly by phosphorylation and augmentation of P450 activity. Thus, these long-chain fatty acids may, infact act at the level of gene/oncogene expression in producing their cytotoxic action on tumour cells. (C) 1999 Harcourt Publishers Ltd.