Fig. 3: Impaired translation of APOE in S181A KI mice, leading to dyslipidemia. | Nature Communications

Fig. 3: Impaired translation of APOE in S181A KI mice, leading to dyslipidemia.

From: Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease

Fig. 3

a RNC-Seq was performed with H9C2 cells treated with Tat-Pep8 or Tat-Pep8-S. Differentially expressed genes (p value <0.05, fold change >2, two-tailed unpaired Student’s t-test) were analyzed for enriched biological processes via Gene Ontology. b RBM24-expressing H9C2 cells were subjected to immunoprecipitated with an anti-RBM24 antibody or IgG. The levels of indicated transcripts in immunocomplexes were determined by RT-PCR analysis (n = 3). c H9C2 cells were treated with Tat-Pep8 or scrambled Tat-Pep8-S for 24 h, followed by WB (n = 3). d Cells were treated with RBM24 siRNA or scrambled siRNA, then exposed to l-azidohomoalaine (AHA) and incubated with biotin/alkyne reaction buffer. Modified proteins were pulled down and analyzed by WB (n = 3). e Tat-Pep8 increased the translation of APOE. The experiment was as in (d) except that cells were treated with peptides for 24 h (n = 3). f, g SI and CVS increased APOE expression along with activation of S181 phosphorylation in mouse hearts. Mice were subjected to social isolation (SI) or group housing (GH) for 30 days (f), and CVS (chronic variable stress) or NS (non-stress) for 30 days (g) (n = 3). h, i SI increased the serum levels of total cholesterol (h) and LDL cholesterol (i) in A/A mice fed with HFD, (n = 5), Three-way ANOVA with Bonferroni post hoc correction for multiple comparisons. j Representative images of Masson’s trichrome-stained heart sections (left) from (h, i) and corresponding quantification (right). Scale bars, 50 μm, (n = 5), Two-way ANOVA with Bonferroni post hoc correction for multiple comparisons. k CVS increased APOE expression along with activation of S181 phosphorylation in mouse liver, (n = 3). l, m APOE overexpression decreased the serum levels of total cholesterol (l) and LDL cholesterol (m) induced by CVS in S181A KI mice (n = 6), One-way ANOVA with Tukey’s posttest. n Verification of HA-tagged APOE expression for (l, m) (n = 3). Data were shown as mean ± SD (h–j, l, m) from five to six independent experiments.

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