ABSTRACT
This study was designed to explore the protective effect of D4F, an apolipoprotein A-I mimetic peptide, on nuclear factor-κB (NF-κB)-dependent Fas/Fas ligand (FasL) pathway-mediated apoptosis in macrophages induced by oxidized low-density lipoprotein (ox-LDL). Our results showed that ox-LDL induced apoptosis, NF-κB P65 nuclear translocation and the upregulation of Fas/FasL pathway-related proteins, including Fas, FasL, Fas-associated death domain proteins (FADD), caspase-8 and caspase-3 in RAW264.7 macrophages, whereas silencing of Fas blocked ox-LDL-induced macrophage apoptosis. Furthermore, silencing of P65 attenuated macrophage apoptosis and the upregulation of Fas caused by ox-LDL, whereas P65 expression was not significantly affected by treatment with Fas siRNA. D4F attenuated the reduction of cell viability and the increase in lactate dehydrogenase leakage and apoptosis. Additionally, D4F inhibited ox-LDL-induced P65 nuclear translocation and upregulation of Fas/FasL pathway-related proteins in RAW264.7 cells and in atherosclerotic lesions of apoE-/- mice. However, Jo2, a Fas-activating monoclonal antibody, reversed the inhibitory effect of D4F on ox-LDL-induced cell apoptosis and upregulation of Fas, FasL and FADD. These data indicate that NF-κB mediates Fas/FasL pathway activation and apoptosis in macrophages induced by ox-LDL and that D4F protects macrophages from ox-LDL-induced apoptosis by suppressing the activation of NF-κB and the Fas/FasL pathway.
Subject(s)
Apolipoprotein A-I/pharmacology , Apoptosis/drug effects , Fas Ligand Protein/metabolism , Foam Cells/drug effects , Foam Cells/metabolism , NF-kappa B/metabolism , Signal Transduction/drug effects , fas Receptor/metabolism , Animals , Apolipoproteins E/deficiency , Diet, High-Fat , Foam Cells/pathology , Lipoproteins, LDL/pharmacology , Mice , Protein Transport , RAW 264.7 CellsABSTRACT
OBJECTIVE: To Compare clinical therapeutic effect of improved thunder-fire miraculous needle and moxibustion on vertigo. METHODS: One hundred and seventeen cases conformed with the TCM criteria of vertigo were randomly divided into an observation group (n=66) and a control group (n=51). The observation group were treated with improved thunder-fire miraculous needle and the control group with pressing and moxibustion at Baihui (GV 20). After treatment of one therapeutic course, the therapeutic effect was assessed by vertigo symptom rating scores. RESULTS: The total effective rate was 86.4% in the observation group and 66.7% in the control group, with a significant difference between the two groups (P<0.05). CONCLUSION: The improved thunder-fire miraculous needle can significantly relieve and eliminate symptoms of vertigo, with no adverse effect.
