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. 2023 Jul 10;12:e82597. doi: 10.7554/eLife.82597

Figure 9. Metabolomic analysis of molidustat treatment in normoxia and hypoxia.

(A) Principal component analysis of intracellular metabolites following 72 hr of treatment suggests a dominant effect of hypoxia over pharmacologic PHD inhibition on the metabolome (n=7). (B) Volcano plot of intracellular metabolites of BAY-treated cells cultured in 21% or 0.5% oxygen. Filled circles indicate significantly increased (blue) and decreased (red) levels in hypoxia. (C) Metabolite set enrichment analysis of metabolites from (B). All KEGG pathways with p-values <0.05 are shown. (D) Leading edge analysis of the TCA cycle metabolite set. Negative values indicate the relative enrichment associated with BAY treatment alone compared to BAY plus hypoxia treatment. Abbreviations: PYR, pyruvate; SUC, succinate; PEP, phosphoenolpyruvate; CIT, citrate; AKG, α-ketoglutarate; MAL, malate; ACO, aconitate; FUM, fumarate.

Figure 9—source data 1. Source data for Figure 9C.

Figure 9.

Figure 9—figure supplement 1. Metabolomic profiling of hypoxia and BAY treated lung fibroblasts.

Figure 9—figure supplement 1.

(A) Volcano plot of differentially regulated metabolites following 0.5% oxygen culture. (B) Volcano plot of differentially regulated metabolites by BAY treatment in 21% oxygen. (C) Venn diagram illustrating the overlap among metabolites differentially regulated by hypoxia (blue) or BAY treatment (purple). (D) Metabolite enrichment in KEGG pathways following hypoxia. (E) Metabolite enrichment in KEGG pathways following BAY. Only significantly enriched metabolite sets with p<0.05 are shown. NES, normalized enrichment score.
Figure 9—figure supplement 1—source data 1. Source data for Figure 9—figure supplement 1D.
Figure 9—figure supplement 1—source data 2. Source data for Figure 9—figure supplement 1E.
Figure 9—figure supplement 2. Changes in NAD(H) and NADP(H) following hypoxia and BAY treamtent.

Figure 9—figure supplement 2.

(A) NAD+, (B) NADH, and (C) NADH/NAD+ from LFs cultured for 72 hr in 0.5% oxygen ±BAY (n=5).(D) NADP+, (E) NADPH, and (F) NADPH/NADP+ from LFs cultured for 72 hr in 0.5% oxygen ±BAY (n=4). Data are mean ± SEM (p<0.05 with black * indicating a significant effect of oxygen within a given treatment and colored * indicating a significant effect of treatment within a given oxygen tension as denoted by the color).