ABSTRACT
Dairy polar lipids (PL) seem to exhibit antiplatelet effects. However, it is not known what molecular species may be responsible. In this study, we confirmed using C30 reversed-phase (C30RP) ultra-high-performance liquid chromatography (UHPLC) coupled to high resolution accurate mass tandem mass spectrometry (HRAM-MS/MS) that fermentation of yoghurts from ovine milk using specific starter cultures altered the PL composition. These lipid alterations occurred concomitant with increased antithrombotic properties of the yoghurts PL fractions against platelet-activating factor (PAF) and thrombin-induced platelet aggregation. Specifically, elevation in phosphatidylethanolamine (PE), sphingomyelin (SM), phosphatidylcholine (PC) and their molecular species were observed following yoghurt fermentation. Furthermore, PC(18:0/18:1), PE(18:1/18:2), SM(d18:0/22:0) and several other molecular species were significantly inversely correlated with the inhibition of PAF and thrombin. These molecular species were abundant in the most bioactive yoghurts fermented by S. thermophilus and L. acidophilus, which suggest that fermentation by these microorganisms increases the antithrombotic properties of ovine milk PL.
Subject(s)
Lipids/analysis , Milk/metabolism , Platelet Aggregation Inhibitors/analysis , Yogurt/analysis , Animals , Blood Platelets/drug effects , Blood Platelets/metabolism , Chromatography, High Pressure Liquid , Fermentation , Lipids/pharmacology , Phosphatidylcholines/metabolism , Phosphatidylethanolamines/metabolism , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Sheep , Sphingomyelins/metabolism , Tandem Mass Spectrometry , Thrombin/pharmacologyABSTRACT
To the best of our knowledge, the present study is the first to demonstrate that treatment of vemurafenib-resistant SKMEL28 (SKMEL28-R) cells with paclitaxel leads to a shift in localization of the E3-ligase BBAP from the cytoplasm to the nucleus, consequently decreasing the metastatic ability of this cell line. The present study revealed that the movement of BBAP from the cytoplasm to nucleus initiated a change in cell morphology. In addition, the translocation of BBAP led to a decrease of metastatic characteristics in SKMEL28R cells, including migration and invasion via downregulation of the phosphorylated form of focal adhesion kinase and Ncadherin, as well as an upregulation of p21 and E-cadherin. The results of the present study suggested that BBAP may not only be a novel biomarker for melanoma, but also a novel therapeutic target for treatment of metastatic melanoma.
