This study was conducted to explore the effect of zerumbone, isolated from Zingiberzerumbet Smith, on apolipoprotein A-I (apoA-I)-mediated cholesterol efflux from THP-1 macrophages. THP-1 macrophages were treated with different concentrations (10-100 μmol/l) of zerumbone and cholesterol efflux was measured. The involvement of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 and ERK1/2 signaling was checked. Notably, zerumbone caused a concentration-dependent induction of ABCA1 but not ABCG1, coupled with enhanced phosphorylation of ERK1/2. Pre-treatment with PD98059 (a potent ERK1/2 inhibitor) significantly blocked the upregulation of ABCA1 by zerumbone. Small interfering RNA-mediated downregulation of ABCA1 but not ABCG1 significantly impaired the promotion of apoA-I-mediated cholesterol efflux by zerumbone. Taken together, zerumbone has the capacity to facilitate apoA-I-mediated cholesterol efflux from macrophages through the activation of ERK1/2 signaling and upregulation of ABCA1.
Coxsackievirus A2 (CVA2) has recently been constantly detected, and is associated with viral myocarditis in children. Our previous study demonstrated that CVA2 led to heart damage in a neonatal murine model. However, the molecular mechanism of heart injury caused by CVA2 remains largely unknown. Emerging evidence suggests the significant functions of miRNAs in Coxsackievirus infection. To investigate potential miRNAs involved in heart injury caused by CVA2, our study, for the first time, conducted a RNA-seq in vivo employing infected mice hearts. In total, 87, 101 and 76 differentially expressed miRNAs were identified at 3 days post infection (dpi), 7 dpi and 7 dpi vs 3 dpi. Importantly, above 3 comparison strategies shared 34 differentially expressed miRNAs. These results were confirmed by quantitative PCR (qPCR). Next, we did GO, KEGG, and miRNA-mRNA integrated analysis of differential miRNAs. The dual-luciferase reporter assay confirmed the miRNA-mRNA pairs. To further confirm the above enriched pathways and processes, we did Western blotting and immunofluorescence staining. Our results suggest that inflammatory responses, T cell activation, apoptosis, autophagy, antiviral immunity, NK cell infiltration, and the disruption of tight junctions are involved in the pathogenesis of heart injury caused by CVA2. The dysregulated miRNAs and pathways recognized in the current study can improve the understanding of the intricate interactions between CVA2 and the heart injury, opening a novel avenue for the future study of CVA2 pathogenesis.
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