Inhibition of neuronal apoptosis by polyunsaturated fatty acids
Inhibition of neuronal apoptosis by polyunsaturated fatty acids
复制标题
DOI：
10.1385/jmn:16:2-3:223
复制
发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
Kim, KY
中科院分区：
文献类型：
--
作者：
Kim, HY;Akbar, M;Kim, KY
使用Neuro-2A和PC-12细胞，基于血清饥饿诱导的DNA片段化和半胱天冬酶-3活性，评价多不饱和脂肪酸（PUFA），二十二碳六烯酸（22：6 n-3; DHA）和花生四烯酸（20：4 n-6; AA）对凋亡性细胞死亡的影响。血清饥饿过程中培养基中20：4 n-6的存在降低了DNA片段化，这种初始保护作用随着血清饥饿时间的延长而减弱。观察到的20：4 n-6的保护作用不受环氧合酶（考克斯）和脂氧合酶抑制剂的影响。相反，22：6 n-3成为保护后，只有富集细胞与此脂肪酸至少24小时前的血清剥夺。在22：6 n-3富集的细胞中，DNA片段化以及半胱天冬酶-3活性降低，同时蛋白质和mRNA水平降低。在富集期，22：6 n-3稳定增加其掺入PS，导致PS总量显著增加; 22：6 n-3的保护作用抑制了PS的积累。细胞直接暴露于18：1 n-9或富集18：1 n-9均无任何保护作用。总之，它提出，20：4 n-6防止神经元凋亡主要是由于非酯化的20：4 n-6，但22：6 n-3的行动，至少部分，通过PS积累。
The effect of polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (22:6n-3; DHA) and arachidonic acid (20 :4n-6; AA), on apoptotic cell death was evaluated based on DNA fragmentation and caspase-3 activity induced by serum starvation using Neuro-2A and PC-12 cells. The presence of 20:4n-6 in the medium during serum starvation decreased DNA fragmentation and this initial protective effect was diminished with prolonged serum starvation. The observed protective effect of 20:4n-6 was not affected by the inhibitors of cyclooxygenase (COX) and lipoxygenase. Conversely 22:6n-3 became protective only after the enrichment of cells with this fatty acid at least for 24 h prior to the serum deprivation. DNA fragmentation as well as caspase-3 activity was reduced in 22:6n-3 enriched cells with a concomitant decrease in protein and mRNA levels. During the enrichment period, 22:6n-3 steadily increased its incorporation into PS leading to a significant increase in the total PS content; the protective effect of 22:6n-3 paralleled the PS accumulation. Neither direct exposure of cells to nor enrichment with 18:1n-9 had any protective effect. In conclusion, it is proposed that 20:4n-6 prevents neuronal apoptosis primarily due to the action of nonesterified 20:4n-6 but 22:6n-3, at least in part, through PS accumulation.