Fig 2: The effects of cell death inhibitors on brain mitochondrial function and brain mitochondrial superoxide dismutase (SOD2) level.A Brain mitochondrial oxidative stress (ROS) level (n = 8–12/group); B brain mitochondrial superoxide dismutase (SOD2) level (n = 6/group); C brain mitochondrial membrane potential changes (n = 8–12/group); D brain mitochondrial swelling (n = 8–12/group). Data are shown as mean ± SEM. *P < 0.05 vs. Sham, †P < 0.05 vs. Cardiac I/R + Vehicle. Veh: cardiac I/R rats treated with vehicle; L: cardiac I/R rats treated with low dose of cell death inhibitor; M: cardiac I/R rats treated with medium dose of cell death inhibitor; H: cardiac I/R rats treated with high dose of cell death inhibitor. I/R ischemia/reperfusion injury.

Fig 3: Parameters of cardiac oxidative stress. (A) Representative immunoblots of uncoupling protein 3 (UCP3); (B) Representative immunoblots of mitochondrial superoxide dismutase (SOD2); (C) Representative immunoblots of mitochondrial superoxide dismutase acetylated on lysine moieties (K-SOD2); (D) Densitometry to red Ponceau S stain. The means represent a consortium of 10 animals per group. GSH: reduced glutathione; GSSG: oxidized glutathione; SIRT3: sirtuin 3; DEF: n-3 PUFA deficient diet; ALA: diet enriched with α-linolenic acid; EPA: diet enriched with eicosapentaenoic acid; Sham: fictive operation; Sept: operation performed to induce sepsis; a, b, c, d, e: means without a common letter in a same figure are significantly different.

Fig 4: Internalized RL2 is localized at mitochondria. MDA-MB-231 cells were stimulated with 100 µg/mL RL2 for indicated time points. Cellular fractionation for cytoplasm (‘C’), nucleus (‘N’) and mitochondria (‘M’) was performed. The fractions were subjected to Western Blot analysis with indicated antibodies. SOD2, Actin, GAPDH and PARP were used as fraction control. The bands corresponding to RL2-Monomer and -Dimer were quantified by ImageLab 5.1 beta (Bio-Rad) from three independent experiments. The statistical analysis was performed by paired student t-test (bottom panel). One representative Western Blot out of three is shown in Figure S4. ns (not significant; p > 0.05), ** (significant; p < 0.01).

Fig 5: Declines in hippocampal volume, neurogenesis, and cognitive function observed in GPR120 KO mice. The level of GPR120 mRNA (A) relative to PGK1 in WT mice tissues, as determined by real-time PCR. Genotyping of GPR120 gene in small intestine, colon, and epididymal adipose tissue (B). Cortical (C) and Hippocampal (D) volumes of WT and GPR120 KO mice. Nissl staining and pyramidal cell counts of hippocampus (E). Scale bar = 80 μm. The protein level determined by western blot analysis (F). The protein level of DCX in the hippocampus (G). The immunofluorescence of DCX (H) and DCX-positive cell count in the dentate gyrus (I). Scale bar = 80 μm. Ki67 staining (J) and the number of Ki67-positive nuclei in the dentate gyrus (K). Scale bar = 80 μm. The level of SOD2 mRNA (L) and protein (M) expression in the hippocampus. The level of synaptophysin (Syn) (N) and PSD95 (O) protein in the hippocampus. Learning and memory performance were evaluated using the Y-maze (P). Data are presented as the mean ± SEM, n = 5 per group. Statistical analysis was performed using a student’s t test (*p < 0.05; **p < 0.01; ***p < 0.001 vs. WT). Morris water maze test: Escape latency (Q) and Time platform crossed (R). Data are mean ± SEM, n = 10 per group. Statistical analysis was performed using two-way ANOVA followed by post-hoc Tukey test (***p < 0.001 vs. WT)