Figure 6: Regulation of ABCA1 and apoA-I expression via LXRα nuclear translocation. | Nature Communications

Figure 6: Regulation of ABCA1 and apoA-I expression via LXRα nuclear translocation.

From: The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells

Figure 6

(a) Extracellular IPP release in DC left untreated or incubated with 1 μM ZA and/or simvastatin (SIM, 1 μM). Simvastatin abrogated ZA-induced extracellular IPP release. Bars represent the mean±s.e.m. of four experiments (**P<0.01; ANOVA). (b) ABCA1 expression in experimental conditions as in a. ZA increased ABCA1 expression, whereas simvastatin showed the opposite effect and abrogated ZA-induced ABCA1 upregulation. (c) apoA-I expression in experimental conditions, as shown in a. ZA increased apoA-1 expression, whereas simvastatin exhibited the opposite effect and abrogated ZA-induced apoA-I upregulation. apoE was unaffected by ZA and/or simvastatin treatments. (d) LXRα, LXRβ and RXR levels were measured in nuclear extracts from DC incubated in the absence (−) or presence (+) of ZA and/or simvastatin. The LXRα activator TO-901317 (TO, 100 nM for 24 h) was employed as a positive control. ZA increased LXRα protein levels and this effect was antagonized by SIM. LXRβ and RXR were unaffected by ZA and/or simvastatin treatment. β-tubulin and TBP are employed as controls of equal protein loading as indicated. The blots are representative of one out of thee experiments (b–d). (e) Activity of Abca1 and apoA-I promoters in the experimental conditions, as shown in d. ZA increased, whereas simvastatin decreased and antagonized the ZA-induced LXRα transcriptional activity of Abca1 and apoA-I promoters. The bars represent the mean±s.e.m. of three experiments (**P<0.01; ***P<0.001; ANOVA). (f) Abca1 and apoA-I mRNA levels in the experimental conditions, as shown in d. ZA increased the Abca1 and apoA-I mRNA levels, whereas simvastatin had the opposite effect and antagonized ZA-induced upregulation. The bars represent the mean±s.e.m. of three experiments (**P<0.01; ***P<0.001; ANOVA). (g) Evaluation of LXRα binding to LRE in the Abca1 promoter. ZA did not modify LXRα transcriptional activity, whereas IPP induced a dose-dependent upregulation of LXRα-dependent Abca1 transcription. LXRα transcriptional activity in ZA-treated DC and TO-induced LXRα transcriptional activity are reported as positive internal controls. The bars represent the mean±s.e.m. of four experiments (*P<0.001; ANOVA). ANOVA, analysis of variance.

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