Fig. 2: p38 MAPK activation accompanies the early cytotoxic decrease of MUFA-PI.
From: PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling
Fibroblasts were cultivated under diverse cytotoxic conditions for 48 h or as indicated. a Negative correlation (−0.6 > r > −1) between cellular p-p38 MAPK (Thr180/Tyr182) levels (at 48 h) and the proportions of phospholipid (PL) species are shown for the co-regulated lipid network described in Supplementary Fig. 1a. Correlations were calculated for mean p-p38 MAPK levels from three independent experiments. b Heatmap showing time-dependent changes in the activation of p38 MAPK compared to vehicle control for each time point. Representative Western blots are shown in Supplementary Fig. 2a. STS, excluded due to pan-kinase inhibition; gray color for I3M, not determined. c, d Phosphorylation and expression of p38 MAPK (P = 0.99995) (c) and JNK (P = 0.000007) (d). Western blots are representative of five (c) or three (b, d) independent experiments. Data of c is identical to w/o in Supplementary Fig. 13b, 16b and 25a. Mean (b) or mean + s.e.m. and single data (c, d) from n = 1 (b I3M for 24 h), n = 2 (b TNFα for 0.17 h, d for TPG), n = 3 (a, b, d), n = 4 (b, c for CHX, I3M at 48 h), n = 5 (b for 48 h, c) independent experiments. P values given vs. vehicle control; mixed-effects model (REML) + Tukey HSD post hoc tests of log data (c, d). e Counter-regulation of PI(18:1/18:1) ratios and p38 MAPK activation during VAL-induced cell death across cell lines. MCF-7 breast adenocarcinoma cells, HEK293 embryonic kidney cells, primary human monocytes, MM6 acute monocytic leukemia cells, HT29 colon adenocarcinoma cells, HeLa cervical carcinoma cells, HepG2 hepatoma cells, and HUVECs were treated with vehicle or VAL (10 µM) for 48 h. Percentage changes in cellular PI(18:1/18:1) ratios and p-p38 MAPK levels were calculated vs. vehicle (100%), and the difference to the vehicle control is presented. Representative Western blots are shown in Supplementary Fig. 2b. Detailed descriptions of datasets shown in panel e are given in Supplementary Note 2. P values given vs. vehicle control; two-tailed paired student t test.
