Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid
Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid
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DOI：
10.1016/s0027-5107(03)00134-9
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发表时间：
2003-09-29
影响因子：
2.3
通讯作者：
Green, IC
中科院分区：
文献类型：
--
作者：
Beeharry, N;Lowe, JE;Green, IC
多不饱和脂肪是脂质过氧化和随后形成致突变代谢物的主要目标，但饱和脂肪含量高的饮食与不良健康影响的关系更为密切。我们发现，在胰岛素分泌细胞系和原代人成纤维细胞中，常见的饱和脂肪酸棕榈酸是一种有效的DNA损伤诱导剂。损伤与诱导型一氧化氮合酶的上调无关，但可以通过两种不同的抗氧化剂，α -硫辛酸和3,3'-甲氧基盐mn (III) （EUK134）来预防，这也部分阻止了棕榈酸诱导的细胞凋亡和生长抑制。由于致突变代谢物可由多不饱和脂肪酸的过氧化作用形成，因此棕榈酸和多不饱和脂肪酸共同施用可能特别有害。相反，棕榈酸引起的DNA损伤是由亚油酸预防的，亚油酸在这里是一种抗氧化应激的保护剂，而不是诱变代谢物的来源。这些结果说明了膳食脂肪摄入与遗传毒性关系的复杂性。(C) 2003 Elsevier B.V.版权所有
Polyunsaturated fats are the main target for lipid peroxidation and subsequent formation of mutagenic metabolites, but diets high in saturated fats are more strongly associated with adverse health effects. We show that the common saturated fatty acid, palmitic acid, is a potent inducer of DNA damage in an insulin-secreting cell line, and in primary human fibroblasts. Damage is not associated with upregulation of inducible nitric oxide synthase, but is prevented by two different antioxidants, alpha-lipoic acid and 3,3'-methoxy salenMn (III) (EUK134), which also partly prevent palmitic acid-induced apoptosis and growth inhibition. Since mutagenic metabolites can be formed from peroxidation of polyunsaturated fatty acids, co-administration of palmitic and a polyunsaturated fatty acid might be particularly harmful. Palmitic acid-induced DNA damage is instead prevented by linoleic acid, which is acting here as a protective agent against oxidative stress, rather than as a source of mutagenic metabolites. These results illustrate the complexity of the relationship of dietary fat intake to genotoxicity. (C) 2003 Elsevier B.V. All rights reserved.