CNR‑ICRM Institute of 'Chemistry of Molecular Recognition', c/o Institute of Biochemistry and Clinical Biochemistry, Catholic University Medical School, I‑00168 Rome, Italy.
Institute of Biochemistry and Clinical Biochemistry, Catholic University Medical School, I‑00168 Rome, Italy.
Int J Mol Med. 2019 Jun;43(6):2523-2531. doi: 10.3892/ijmm.2019.4170. Epub 2019 Apr 23.
Docosahexaenoic acid (DHA) is an omega‑3 polyunsaturated fatty acid, derived mainly from fish oil. It is well known that DHA is present in high concentrations in nervous tissue and plays an important role in brain development and neuroprotection. However, the molecular mechanisms underlying its role remain to be fully elucidated. In this study, to enhance our understanding of the pathophysiological role of DHA, we investigated the possible neuroprotective mechanisms of action of DHA against hydrogen peroxide (H2O2)‑induced oxidative damage in a rat pheochromocytoma cell line (PC12). Specifically, we evaluated the viability, oxidation potential, and the expression and production of antioxidant/cytoprotective enzymes, and eventual apoptosis. We found that pre‑treatment with DHA (24 h) protected the cells from H2O2‑induced oxidative damage. In particular, pre‑treatment with DHA: i) Antagonized the consistent decrease in viability observed following exposure to H2O2 for 24 h; ii) reduced the high levels of intracellular reactive oxygen species (ROS) associated with H2O2‑induced oxidative stress; iii) increased the intracellular levels of enzymatic antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GSH‑Px)] both under basal conditions and following H2O2 exposure; iv) augmented the intracellular levels of reduced glutathione (GSH) and ascorbic acid, while it reduced the malondialdehyde (MDA) levels under conditions of oxidative stress; v) upregulated the expression of nuclear factor (erythroid‑derived 2)‑like 2 (NFE2L2) and its downstream target protein, heme‑oxygenase‑1 (HO‑1); and vi) induced an anti‑apoptotic effect by decreasing Bax and increasing Bcl2 expression. These findings provide evidence suggesting that DHA is able to prevent H2O2‑induced oxidative damage to PC12 cells, which is attributed to its antioxidant and anti‑apoptotic effects via the regulation NFE2L2/HO‑1 signaling. Therefore, DHA may play protective role in neurodegenerative diseases associated with oxidative stress.
二十二碳六烯酸（DHA）是一种ω-3 多不饱和脂肪酸，主要来源于鱼油。众所周知，DHA 大量存在于神经组织中，在大脑发育和神经保护中发挥着重要作用。然而，其作用的分子机制仍有待充分阐明。在这项研究中，为了增强我们对 DHA 病理生理学作用的理解，我们研究了 DHA 对过氧化氢（H2O2）诱导的大鼠嗜铬细胞瘤细胞系（PC12）氧化损伤的可能神经保护作用机制。具体而言，我们评估了细胞活力、氧化电位以及抗氧化/细胞保护酶的表达和产生，以及最终的细胞凋亡。我们发现，DHA（24 小时）预处理可保护细胞免受 H2O2 诱导的氧化损伤。特别是，DHA 预处理：i）拮抗了暴露于 H2O2 24 小时后观察到的细胞活力持续下降；ii）降低了与 H2O2 诱导的氧化应激相关的高水平细胞内活性氧（ROS）；iii）在基础条件下和暴露于 H2O2 后，均增加了细胞内酶抗氧化剂[超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）]的水平；iv）在氧化应激条件下增加了还原型谷胱甘肽（GSH）和抗坏血酸的细胞内水平，同时降低了丙二醛（MDA）水平；v）上调了核因子（红系衍生 2）样 2（NFE2L2）及其下游靶蛋白血红素加氧酶 1（HO-1）的表达；vi）通过降低 Bax 并增加 Bcl2 表达来诱导抗凋亡作用。这些发现表明，DHA 能够防止 H2O2 诱导的 PC12 细胞氧化损伤，这归因于其通过调节 NFE2L2/HO-1 信号通路的抗氧化和抗凋亡作用。因此，DHA 可能在与氧化应激相关的神经退行性疾病中发挥保护作用。
