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. 2022 May 20:185:1-5.
doi: 10.1016/j.freeradbiomed.2022.04.002. Epub 2022 Apr 18.

Neuroprotective effects of DHA-derived peroxidation product 4(RS)-4-F4t-neuroprostane on microglia

Xue Geng  1 , Jean-Marie Galano  2 , Camille Oger  2 , Grace Y Sun  3 , Thierry Durand  2 , James C Lee  4
Affiliations

Neuroprotective effects of DHA-derived peroxidation product 4(RS)-4-F4t-neuroprostane on microglia

Xue Geng et al. Free Radic Biol Med. .

Abstract

The abundance of docosahexaenoic acid (DHA) in brain membrane phospholipids has stimulated studies to explore its role in neurological functions. Upon released from phospholipids, DHA undergoes enzymatic reactions resulting in synthesis of bioactive docosanoids and prostanoids. However, these phospholipids are also prone to non-enzymatic reactions leading to more complex pattern of metabolites. A non-enzymatic oxidized product of DHA, 4(RS)-4-F4t-Neuroprostane (44FNP), has been identified in cardiac and brain tissues. In this study, we examined effects of the 44FNP on oxidative and inflammatory responses in microglial cells treated with lipopolysaccharide (LPS). The 44FNP attenuated LPS-induced production of reactive oxygen species (ROS) in both primary and immortalized microglia (BV2). It also attenuated LPS-induced inflammation through suppressing NFκB-p65 and levels of iNOS and TNFα. In addition, 44FNP also suppressed LPS-induced mitochondrial dysfunction and upregulated the Nrf2/HO-1 antioxidative pathway. In sum, these findings with microglial cells demonstrated neuroprotective effects of this 44FNP and shed light into the potential of nutraceutical therapy for neurodegenerative diseases.

Keywords: 4(RS)-4-F4t-Neuroprostane; Antioxidant, and anti-inflammatory; Microglia.

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Figures

Fig. 1.
Fig. 1.
44FNP attenuated LPS-induced reactive oxygen species (ROS) production in primary mouse microglia and BV2 cells. Primary microglia (A), BV2 cells (B) were pretreated with 44FNP for 1 h, followed by stimulation with 50 ng/ml LPS for 12 h. Data are represented in mean ± standard deviation (SD) (n = 3). Statistical analysis was carried out with one way ANOVA followed by Bonferroni post-tests. *p < 0.05, **p < 0.01, ***p < 0.001 compared with the LPS group; ###p < 0.001, ####p < 0.0001 compared with the control group.
Fig. 2.
Fig. 2.
44FNP attenuated LPS-triggered the p65 pathway (A), iNOS (B), TNF-α (C) in BV2 cells. BV2 cells were pretreated with 44FNP for 1 h followed by stimulation with 50 ng/ml LPS for 1 h (A) or 18 h (B, C). Data are represented in mean ± SD (n = 3). Statistical analysis was carried out with one way ANOVA followed by Bonferroni post-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared with the LPS group; ###p < 0.001, ####p < 0.0001 compared with the control group.
Fig. 3.
Fig. 3.
44FNP attenuated LPS-induced mitochondrial membrane potential loss in BV2 cells. Cells were pretreated with 44FNP for 1 h followed by stimulation with 50 ng/ml LPS for 24 h. Data are represented in mean ± SD (n = 3). Statistical analysis was carried out with one way ANOVA followed by Bonferroni post-tests. *p < 0.05, **p < 0.01, ***p < 0.001 compared with the LPS group; ##p < 0.01, ####p < 0.0001 compared with the control group.
Fig. 4.
Fig. 4.
44FNP enhanced LPS-induced Nrf2/HO-1 pathway in BV2 cells. Cells were pretreated with 44FNP for 1 h followed by stimulation with 50 ng/ml LPS for 6 h. Data are represented in mean ± SD (n = 3). Statistical analysis was carried out with one way ANOVA followed by Bonferroni post-tests. #p < 0.05, ##p < 0.01, ###p < 0.001 compared with the control group.
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