ABSTRACT
Astragaloside III (AS-III) is a triterpenoid saponin contained in Astragali Radix and has potent anti-inflammatory effects on vascular endothelial cells; however, underlying mechanisms are unclear. In this study, we provided the first piece of evidence that AS-III induced phosphorylation of TNF-α converting enzyme (TACE) at Thr735 and enhanced its sheddase activity. As a result, AS-III reduced surface TNFR1 level and increased content of sTNFR1 in the culture media, leading to the inhibition of NF-κB signaling pathway and attenuation of downstream cytokine gene expression. Furthermore, AS-III induced TACE-dependent epidermal growth factor receptor (EGFR) transactivation and activation of downstream ERK1/2 and AKT pathways. Finally, AS-III induced activation of p38. Both TACE activation and EGFR transactivation induced by AS-III were significantly inhibited by p38 inhibitor SB203580. Taken together, we concluded that AS-III activates TACE-dependent anti-inflammatory and growth factor signaling in vascular endothelial cells in a p38-dependent fashion, which may contribute to its cardiovascular protective effect.
Subject(s)
ADAM17 Protein/drug effects , Endothelial Cells/drug effects , Saponins/therapeutic use , Animals , Humans , Mice , Saponins/pharmacology , Signal Transduction/drug effectsABSTRACT
Circular RNA (circRNA) is a new endogenous transcription product, which has attracted significant attention in RNA biology research.CircRNA comprise exons or introns involved in regulation of various mechanisms.These molecules are stable and species-specific, as well as cell and tissue-specific.Cardiovascular diseases particularly myocardial ischemia and ageing-related diseases, pose a major health care burden and novel treatments and biomarkers should be explored.Recent findings indicate that circRNAs are implicated in biological processes, such as glucose metabolism, fatty acid oxidation, mitochondrial biosynthesis, implying that they are potential targets for myocardial ischemia treatment.In the present review, the functions of circRNAs in the heart are described, with emphasis given on in the relationship with myocardial ischemia and cardiac aging-related diseases.Directions for future research are also summarized.