ABSTRACT
BACKGROUND: ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor-B1 (SR-B1) promote cholesterol efflux from cells to lipid-poor apolipoprotein A-I and play an important role in the development of atherosclerosis. Liver X receptor (LXRα) and peroxisome proliferator-activated receptor-gamma (PPARγ) operate as cholesterol sensors, which may protect from cholesterol overload by stimulating cholesterol efflux from cells to high-density lipoprotein through ABCA1, ABCG1, and SR-B1. Propofol administration is associated with cardiovascular protective effects, including anti-inflammatory and antioxidant properties. Here, we examined the effect of propofol on ABCA1, ABCG1, and SR-B1 expression and explored whether PPARγ and LXRα were involved in the regulation of propofol-induced ABCA1, ABCG1, and SR-B1 expression in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: Propofol significantly increased expression levels of ABCA1, ABCG1, and SR-B1 in a time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by propofol treatment. Moreover, PPARγ and LXRα were up-regulated by propofol treatment. In addition, the up-regulated expression of ABCA1, ABCG1, and SR-B1 by propofol was significantly abolished by both PPARγ siRNA and LXRα siRNA in THP-1 macrophage-derived foam cells. CONCLUSION: These results provide evidence that propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα pathway in THP-1 macrophage-derived foam cells.
Subject(s)
ATP Binding Cassette Transporter 1/metabolism , ATP-Binding Cassette Transporters/metabolism , Anticholesteremic Agents/pharmacology , Foam Cells/drug effects , Orphan Nuclear Receptors/metabolism , PPAR gamma/metabolism , Propofol/pharmacology , Scavenger Receptors, Class B/metabolism , Signal Transduction/drug effects , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 1 , ATP-Binding Cassette Transporters/genetics , Cell Line , Cholesterol/metabolism , Foam Cells/metabolism , Humans , Liver X Receptors , Orphan Nuclear Receptors/genetics , PPAR gamma/genetics , RNA Interference , RNA, Messenger/metabolism , Scavenger Receptors, Class B/genetics , Time Factors , Transfection , Up-RegulationABSTRACT
Monocyte chemoattractant protein-1 (MCP-1) is a cytokine that mediates the influx of cells to sites of inflammation. Our group recently reported that propofol exerted an anti-inflammatory effect and could inhibit lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines. However, the effect and possible mechanisms of propofol on MCP-1 expression remain unclear. LPS-stimulated HepG2 cells were treated with 50 µM propofol for 0, 6, 12, and 24 h, respectively. The transcript and protein levels were measured by real-time quantitative PCR and Western blot analyses, respectively. We found that propofol markedly decreased both MCP-1 messenger RNA (mRNA) and protein levels in LPS-stimulated HepG2 cells in a time-dependent manner. Expression of apolipoprotein M (apoM) and forkhead box protein A2 (foxa2) was increased by propofol treatment in HepG2 cells. In addition, the inhibitory effect of propofol on MCP-1 expression was significantly abolished by small interfering RNA against apoM and foxa2 in LPS-stimulated HepG2 cells. Propofol attenuates LPS-induced MCP-1 production through enhancing apoM and foxa2 expression in HepG2 cells.
Subject(s)
Anesthetics, Intravenous/pharmacology , Apolipoproteins/biosynthesis , Chemokine CCL2/biosynthesis , Hepatocyte Nuclear Factor 3-beta/biosynthesis , Lipocalins/biosynthesis , Propofol/pharmacology , Anti-Inflammatory Agents/pharmacology , Apolipoproteins/genetics , Apolipoproteins M , Cell Line , Cell Movement , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Hep G2 Cells , Hepatocyte Nuclear Factor 3-beta/genetics , Humans , Lipocalins/genetics , Lipopolysaccharides , RNA Interference , RNA, Messenger/biosynthesis , RNA, Small InterferingABSTRACT
Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 µM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 µM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.
Subject(s)
Microsomes, Liver/metabolism , Trifluoperazine/pharmacokinetics , Animals , Humans , Macaca fascicularis , Species SpecificityABSTRACT
Review the research and development status that Chinese medicine are compatible with Tripterygium wilfordii for attenuation and synergy for recent year. From modern medicine view and Chinese medicine dialectical perspective explain the mechanisms and methods of compatibility applied to attenuation and synergy of T. wilfordii. Provide a reference for reasonable application of other toxic Chinese medicine. Prefer the suggestion that Chinese medicinal formulae can be developed into Chinese medicine compound preparation.
