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[Preprint]. 2023 Jan 10:2023.01.05.522933. [Version 2] doi: 10.1101/2023.01.05.522933

Figure 3. EED, epoxy metabolites downstream of DGLA, induce neurodegeneration by ferroptosis.

Figure 3.

(A) DGLA is metabolized to EED and DHED through the CYP and epoxide hydrolase enzymes, respectively; and AUDA inhibits epoxide hydrolase; (B) Oxylipin profile representing the pmol/g of EED and DHED regioisomers in worms treated with 100 μM of DGLA ± 100 μM AUDA compared to control (C) Percentage (%) of worms with healthy ADE neurons for Pdat-1::gfp treated with 100 μM of DGLA ± 100 μM AUDA; (D) Percentage (%) of worms with healthy ADE neurons for Pdat-1::gfp worms treated with 100 μM DGLA and 100 μM EED; (E) Dose response curve: the effect of different concentration of EED on degeneration of ADE neurons on Day 1 and Day 8 adulthood; (F) Percentage (%) of worms with healthy ADE neurons in Pdat-1::gfp worms treated with 100 μM of different Ep-PUFAs, EpOME, and EEQ; (G) Percentage (%) of worms with healthy ADE neurons of worms treated with 100 μM DGLA ± 100 μM Liproxstatin-1;(H) Comparison the effect of 250 μM Liproxstatin-1 on Pdat-1::gfp worms treated with 100 μM of DGLA compared to 100 μM EED;(I) Percentage (%) of worms with healthy ADE neurons with Pdat-1::gfp and Pdat-1::gfp;ced-3 worms treated with 100 μM; (J) Percentage (%) of worms with healthy ADE neurons for Pdat-1::gfp and Pdat-1::gfp; ftn-1 worms treated with 100 μM DGLA; All supplementations were done at the L4 stage. Two-way analysis of variance (ANOVA), Tukey’s multiple comparison test. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P < 0.0001, without * not significant. DGLA: Dihomo-γ-linolenic acid, EED: epoxyeicosadienoic acids, DHED: dihydroxyeicosadienoic acids, CYP: Cytochrome P450, EH: epoxide hydrolase, AUDA: 12-(1-adamantane-1-yl-ureido-) dodecanoic acid, Lip-1: Liproxstatin-1, EpOME: epoxyoctadecenoic acids; EEQ: epoxyeicosatetraenoic acid.