Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Aβ1-42
Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Aβ1-42
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DOI：
10.1016/j.neuropharm.2008.02.003
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发表时间：
2008-05-01
影响因子：
4.7
通讯作者：
Williams, Alun
中科院分区：
文献类型：
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作者：
Bate, Clive;Marshall, Victoria;Williams, Alun
含有多不饱和脂肪酸(PUFA)的膳食补充剂经常被认为对健康有好处，包括可能减少老年人的认知能力下降。在这里，我们报告了用二十二碳六烯酸(DHA)或二十碳五烯酸(EPA)的预处理显著降低了与HuPrP82-146或Aβ(1-42)孵育的皮质或小脑神经元的存活率，HuPrP82-146是一种源自PrP82-146的多肽，Aβ(1-42)是一种在阿尔茨海默病中发现的多肽。用DHA或EPA处理可降低神经细胞膜的游离胆固醇含量。这并不影响神经元摄取FITC-HuPrP82-146的量，但增加了掺入动力学。在未经处理的神经元中，FITC-HuPrP82-146迁移到含有小窝蛋白-1的脂筏上。HuPrP82-146的加入还触发了胞质磷脂酶A(2)(CPLA(2))向含有小窝蛋白-1的木筏的迁移，并增加了前列腺素E(2)的产量。经DHA处理的神经元，CPLA(2)的活性和前列腺素E(2)的产生均增加。这些结果与DHA或EPA改变细胞膜导致HuPrP82-146定位于含有小窝蛋白-1的筏子的数量增加，CPLA(2)的激活，前列腺素E(2)的产生，caspase-3的活性和神经元存活的减少是一致的。这些观察结果提出了这样一种可能性，即一些多不饱和脂肪酸补充剂可能会加速Prion或阿尔茨海默病晚期的神经元丢失。(C)2008爱思唯尔有限公司。保留所有权利。
Dietary supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including a possible reduction in cognitive decline in the elderly. Here we report that pre-treatment with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) significantly reduced the survival of cortical or cerebellar neurons incubated with HuPrP82-146, a peptide derived from the prion protein, or with A beta(1-42), a peptide found in Alzheimer's disease. Treatment with DHA or EPA reduced the free cholesterol content of neuronal membranes. This did not affect the amount of FITC-HuPrP82-146 ingested by neurons, but increased the kinetics of incorporation. In untreated neurons, FITC-HuPrP82-146 migrated to caveolin-1 containing lipid rafts. The addition of HuPrP82-146 also triggered the migration of cytoplasmic phospholipase A(2) (cPLA(2)) into caveolin-1 containing rafts, and increased prostaglandin E(2) production. Activation of cPLA(2) and prostaglandin E(2) production were both increased in neurons pre-treated with DHA. These results are consistent with DHA or EPA altering cell membranes resulting in increased amounts of HuPrP82-146 localising to caveolin-1 containing rafts, increased activation of cPLA(2), prostaglandin E(2) production, caspase-3 activity and reduced neuronal survival. Such observations raise the possibility that some PUFA supplements may accelerate neuronal loss in the terminal stages of prion or Alzheimer's diseases. (C ) 2008 Elsevier Ltd. All rights reserved.