Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA
Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA
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DOI：
10.1007/s12017-018-8496-8
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Martin-Fernandez, Beatriz
中科院分区：
文献类型：
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作者：
Belen Ruiz-Roso, Maria;Olivares-Alvaro, Elena;Martin-Fernandez, Beatriz
二十二碳六烯酸(DHA，22：6n-3)是神经细胞膜上一种必需的omega-3(omega-3)长链多不饱和脂肪酸，参与正常的生长、发育和功能。DHA已被提出用来减少神经退行性变过程中的有害影响。尽管如此，DHA的临床和临床前研究结果中的一些不一致可能归因于标准DHA治疗中存在植酸(PHA)。因此，我们研究的目的是分析和比较低浓度DHA和标准浓度DHA在不同神经毒性条件下对BV-2激活的小胶质细胞的影响。为此，用脂多糖或过氧化氢刺激小鼠小胶质细胞BV-2，并与50ppm的DHA(PHA：50)或500ppm的DHA(PHA：500)共同孵育。检测细胞存活率、超氧阴离子(O-2(-))生成、白介素6(L-6)、环氧合酶-2(COX-2)、诱导型一氧化氮合酶(INOS)、谷胱甘肽过氧化物酶(GtPx)、谷胱甘肽还原酶(GtRd)、半胱氨酸天冬氨酸氨基转移酶-3(Caspase-3)及脑源性神经营养因子(BDNF)蛋白表达。与DHA(PHA：500)相比，低PHA浓度的DHA可保护BV-2激活的细胞免受内毒素或H_2O_2诱导的细胞活力下降和O-2(-)产生减少。与DHA(PHA：500)相比，低PHA浓度的DHA还降低了COX-2、IL-6、iNOS、GtPx、GtRD和SOD-1的蛋白表达。此外，与DHA(PHA：500)相比，低PHA浓度的DHA增加了BDNF蛋白的表达。这项研究提供的数据支持，与激活的小胶质细胞中标准的PHA浓度的DHA相比，低浓度的DHA在神经毒性损伤中的有益效果。
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (omega-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O-2 (-)) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H2O2-induced cell viability reduction in BV-2 activated cells and O-2 (-) production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.