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Fig. 3 Chronic work overload leads to mitochondrial calcium overload.

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Presentation on theme: "Fig. 3 Chronic work overload leads to mitochondrial calcium overload."— Presentation transcript:

1 Fig. 3 Chronic work overload leads to mitochondrial calcium overload.
Chronic work overload leads to mitochondrial calcium overload. (A) Principal component (PC) analysis of RNA sequencing data from the hearts of control and ISO-treated mice (7 days). CPM, continuous phase modulation. (B) Most relevant Ingenuity Canonical Pathways (ICPs) enriched using the differentially expressed genes in OMA1KO ISO versus control. The inner bar circle represents the fold enrichment and the overall changes as a z score. The outer circle displays the logFC of the differentially expressed genes belonging to each category. eNOS, endothelial nitric oxide synthase; mTOR, mammalian target of rapamycin; NO, nitric oxide; iNOS, inducible nitric oxide synthase; ATM, ataxia-telangiectasia mutated. (C) Detailed relationship between changed genes [abs(logFC) ≥ 1 in any contrast] and the pathways selected by Chord Plots [left: logFC of genes in the contrasts ISO versus control of WT (inner) and OMA1KO (outer) mice; right: ICPs connected to the genes]. For (B) and (C), red represents up-regulated genes, and blue represents down-regulated genes. (D) Western blot analysis of mitochondrial lysated and quantification of mitochondrial calcium uniporter (MCU) components (MCU and M1CU1) after short chronic (7 days) ISO administration. (E) Western blot analysis and quantification of MCU expression modulation by mitochondrial ROS (mtROS) after chronic (28 days) ISO administration. (F to H) Effects of mitochondrial fission blockade with Mdivi1. (I to K) Effects of ryanodine receptor 2 (RyR2) activation with caffeine. (L to N) Effects of RyR2 blockade with dantrolene. (F, I, and L) Cardiac contractility (% EF and HR); (G, J, and M) Mitochondrial ATP synthesis; (H, K, and N) OPA1 processing and MCU expression. Loading controls were SDHA, core1, core2, MnSOD, and Tom20. Data are given as scatter dot plots, and lines are means ± SD. Differences assessed by one-way ANOVA and Tukey’s multiple comparison test. N as described in table S1; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < Rebeca Acin-Perez et al., Sci Transl Med 2018;10:eaan4935 Published by AAAS

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