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. 2022 Jan 4;132(1):e151685. doi: 10.1172/JCI151685

Figure 3. 15LO1 expression and activity regulate intracellular redox balance by lowering GSH and GSH:GSSG.

Figure 3

(A) Under IL-13–stimulated conditions, ALOX15 (15LO1) knockdown (KD) increases intracellular GSH and the GSH:GSSG ratio toward control conditions (n = 6). (B) Under IL-13 conditions, inhibition of 15LO1 by the specific 15LO1 inhibitor BLX2477 also restores intracellular GSH and GSH:GSSG (n = 6). (C) ALOX15 KD lowers extracellular GSSG and restores a normal GSH:GSSG ratio (n = 6). (D) Representative Western blots demonstrating that ALOX15 KD also decreases GPX4 protein expression (n = 4). (E) Representative Western blots show decreased expression of GPX4 under conditions of 15LO1 inhibition (n = 4). (F) Ex vivo 15LO1 protein expression correlates with intraepithelial cell GSH and GSH:GSSG (n = 15). (G) Indexing SLC7A11, as a critical regulator of intracellular GSH levels, to 15LO1 improves the relationship of 15LO1 to intracellular GSH (n = 12). Matched-pair analysis (A–C) of log-transformed data was used to compare conditions, while Pearson’s correlation was used for F and G.