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1.
BMC Anesthesiol ; 21(1): 272, 2021 11 08.
Article in English | MEDLINE | ID: mdl-34749669

ABSTRACT

BACKGROUND: Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats. METHODS: Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels. RESULTS: Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1ß and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased. CONCLUSIONS: The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.


Subject(s)
Autonomic Nerve Block/methods , Memory Disorders/therapy , Sleep Deprivation/complications , Stellate Ganglion , Animals , Hippocampus/pathology , Male , Melatonin/blood , Memory Disorders/etiology , Neurons/pathology , Rats , Rats, Sprague-Dawley , Sleep Deprivation/physiopathology , Spatial Learning/physiology
2.
Sleep Breath ; 25(4): 1969-1976, 2021 12.
Article in English | MEDLINE | ID: mdl-33619665

ABSTRACT

BACKGROUND: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. METHODS: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein-protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. RESULTS: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure-based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. CONCLUSIONS: These genes and pathways might become therapeutic targets with clinical usefulness in the future.


Subject(s)
Gene Expression Profiling , Gene Regulatory Networks/genetics , Signal Transduction/genetics , Sleep Deprivation/genetics , Humans
3.
Biochem Biophys Res Commun ; 503(4): 2872-2877, 2018 09 18.
Article in English | MEDLINE | ID: mdl-30100058

ABSTRACT

Protein glycosylation, attaching glycans covalently onto amino acid side chains of protein by various glycosyltransferase, is the most common post-translational modification. The UDP-GalNAc transferase 3 (GANLT3), encoded by Galnt3, transfers N-acetyl-d-galactosamine to hydroxyl groups of the side chains of Ser/Thr residues, initiating mucin type O-glycosylation of proteins. Most researches as yet focus on the involvement and abnormal expression of GALNT3 in various tumors. In this study, we found that GALNT3 was significantly decreased in the lungs after influenza A virus (IAV) infection in mice. Overexpression of GALNT3 in cell lines markedly inhibited IAV replication. Further experiments demonstrated that GALNT3 inhibited NF-κB signaling by preventing the translocation of phosphorylated P65 into nucleus. Therefore, our results reveal an important role of GALNT3 in regulating host responses during IAV infection, indicating the broad functions of the GALNT family, and the direct involvement of GALNTs during viral infections.


Subject(s)
Influenza A virus , N-Acetylgalactosaminyltransferases/physiology , Orthomyxoviridae Infections/enzymology , Active Transport, Cell Nucleus , Animals , Cell Line , Mice , NF-kappa B/metabolism , Orthomyxoviridae Infections/metabolism , Signal Transduction , Transcription Factor RelA/metabolism , Virus Replication , Polypeptide N-acetylgalactosaminyltransferase
4.
Redox Biol ; 16: 255-262, 2018 06.
Article in English | MEDLINE | ID: mdl-29549823

ABSTRACT

OBJECTIVE: Several miR/s that regulate gene/s relevant in atherogenesis are being described. We identified a miR (miR-98) that targets LOX-1, a receptor for ox-LDL, and speculated that it might be relevant in atherogenesis. APPROACH AND RESULTS: MicroRNA-98 was predicted by bioinformatics tools. The effects of miR-98 (by use of mimics and inhibitors) on LOX-1 expression and foam cell formation in mouse peritoneal macrophages were assessed. ApoE-/- mice fed by high fat diet were administered with mmu-agomiR-98 and mmu-antagomiR-98, and expression of LOX-1 and foam cell formation in aorta were quantified. LOX-1 was established to be a direct target of miR-98 by luciferase reporter assay. Enhancement of miR-98 decreased the expression of LOX-1 and inhibited foam cell formation and lipid accumulation. Inhibition of miR-98 had the opposite effects on all parameters. CONCLUSIONS: Reduced expression of miR-98 may relate to LOX-1 expression and foam cell formation and lipid accumulation in aortas of ApoE-/- mice. Plasma level of miR-98 may be a biomarker of atherosclerotic disease process and its modulation may offer a therapeutic strategy for atherosclerosis.


Subject(s)
Apolipoproteins E/genetics , Atherosclerosis/genetics , MicroRNAs/genetics , Scavenger Receptors, Class E/genetics , Animals , Atherosclerosis/blood , Atherosclerosis/pathology , Diet, High-Fat , Foam Cells/metabolism , Gene Expression Regulation , Humans , Lipid Metabolism/genetics , Lipoproteins, LDL/metabolism , Macrophages/metabolism , Mice , Mice, Knockout
5.
Dalton Trans ; 47(2): 348-356, 2018 Jan 02.
Article in English | MEDLINE | ID: mdl-29215106

ABSTRACT

Semiconductor-based photocatalytic hydrogen evolution from water with earth-abundant and low cost co-catalysts has attracted much attention. Herein, novel Cu2(OH)2CO3 decorated 2D TiO2 nanosheets for photocatalytic water splitting were synthesized by a facile in situ synthetic method. The chemical and photophysical properties of Cu2(OH)2CO3/TiO2 nanosheets were investigated by X-ray diffractometry (XRD), transmission electron microscopy (TEM), UV-vis diffusion reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) analysis. At an optimal Cu2(OH)2CO3 loading content of 1.5 mol%, the hybrid photocatalyst delivers a high photocatalytic H2 production rate of 1555.07 µmol g-1 h-1. Such enhanced photocatalytic activity is attributed to tight interfaces formed between Cu2(OH)2CO3 nanoparticles and TiO2 nanosheets, which play a vital role in the separation of photo-excited carriers, and the formation of active Cu1+ and Cu0 species can also benefit the charge separation process by reducing the over-potential of water reduction. Based on the above results, a possible mechanism is proposed and further verified using photoluminescence (PL) spectra. This work may provide more insight into the synthesis of novel Cu2(OH)2CO3/TiO2 nanosheets with high photocatalytic H2 evolution activity for solar-to-chemical conversion and utilization.

6.
Talanta ; 172: 206-214, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28602296

ABSTRACT

High levels of triacylglycerols (TGs) have been linked to cardiovascular disease and liver diseases. Comprehensively analyzing TGs is helpful to understand the TGs functions in these diseases. However, due to the existence of a large number of isomers TGs and the lack of commercial standards, precise analysis of individual triacylglycerol (TG) with specific fatty acid chain composition is full of challenge. In this work, ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization (ESI) mass spectrometry (MS) were employed for comprehensive qualification and quantification of TGs with specific fatty acid chain composition in horse adipose tissue, human plasma and liver tissues including hepatocellular carcinoma (HCC) and para-carcinoma tissues. Multiple MS detection modes from QTRAP MS and FT-ICR MS were utilized, and hundreds of TG species (including many oxidized TG species) with their specific fatty acid chain compositions have been qualified and quantified. The isomer TGs interference, the isobaric interference, and oxidized TG species interference were firstly indicated. Several isomer TGs, for example, 18:1/20:1/18:2 TG and 20:3/18:1/18:0 TG, which were all 56:4 TG, demonstrated different trends in HCC tissue compared with para-carcinoma tissue, which showed the importance of analysis of TG with specific fatty acid chain composition. In addition, 10 TGs with the degree of unsaturation beyond three were significantly decreased, while 16:0/17:0/18:0 TG, no double bond, was significantly increased in the HCC tissue, which firstly revealed aberrant specific TG metabolism in HCC. This is a systematic report about comprehensive analysis of TGs by UPLC-ESI-MS, which is of significance for accurate analysis of these lipids.


Subject(s)
Adipose Tissue/chemistry , Blood Chemical Analysis/methods , Fatty Acids/chemistry , Horses , Liver/chemistry , Triglycerides/blood , Triglycerides/chemistry , Animals , Humans , Spectrometry, Mass, Electrospray Ionization , Triglycerides/analysis
7.
Dalton Trans ; 46(32): 10620-10629, 2017 Aug 15.
Article in English | MEDLINE | ID: mdl-28401230

ABSTRACT

Novel layer-like Ni(OH)2 co-catalyst-decorated ZnIn2S4 microsphere photocatalysts were synthesized for the first time via a facile in situ deposition method to boost the photocatalytic H2-production performance. The physical and optical properties of the as-prepared Ni(OH)2-ZnIn2S4 composite samples were characterized via X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis diffusion reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), and surface photovoltage spectroscopy (SPV). The results indicate that the photocatalytic H2 evolution activity of the ZnIn2S4 microspheres under visible light irradiation significantly enhances by introducing inexpensive Ni(OH)2 as a co-catalyst. The 5 mol% Ni(OH)2-ZnIn2S4 sample shows the highest H2-production rate of 8.35 mmol g-1 h-1, which is 18 times higher than that of pure ZnIn2S4. Moreover, photocatalytic activity of the Ni(OH)2-ZnIn2S4 sample remains stable even after 4 cycling photocatalytic experiments. In addition, a possible mechanism on the enhanced photocatalytic activity was proposed and verified by surface photovoltage spectroscopy.

8.
Sci Rep ; 6: 38228, 2016 12 02.
Article in English | MEDLINE | ID: mdl-27910907

ABSTRACT

MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively. Q-PCR data indicated that ATP4, which was expressed inversely in relation to Cre-miR906-3p under stress conditions. Overexpressing of Cre-miR906-3p enhanced resistance to multiple stresses; conversely, overexpressing of ATP4 produced the opposite effect. These data of Q-PCR, degradome sequencing and adaptation of overexpressing lines indicated that Cre-miR906-3p and its target ATP4 were a part of the same pathway for stress adaptation. We found that Cre-miR910 and its target NCR2 were also a part of this pathway. Overexpressing of Cre-miR910 decreased, whereas that of NCR2 increased the adaption to multiple stresses. Our findings suggest that the two classes of miRNAs synergistically mediate stress adaptation in algae.


Subject(s)
Chlamydomonas reinhardtii/metabolism , Gene Expression Regulation, Plant/physiology , MicroRNAs/biosynthesis , RNA, Plant/biosynthesis , Stress, Physiological/physiology , Chlamydomonas reinhardtii/genetics , MicroRNAs/genetics , Plant Proteins/biosynthesis , Plant Proteins/genetics , RNA, Plant/genetics
9.
Int J Clin Exp Med ; 8(8): 13622-7, 2015.
Article in English | MEDLINE | ID: mdl-26550304

ABSTRACT

BACKGROUND: We evaluated the effects of transcutaneous electric acupoint stimulation (TEAS) on the postoperative quality of recovery after thyroidectomy with general anesthesia in this prospective, randomized, double-blind, placebo-controlled study. METHODS: Eight-four American Society of Anesthesiologists physical status (ASA) I or II patients undergoing thyroidectomy were randomly allocated to TEAS or control groups. The primary outcome was the quality of recovery, which was assessed on the day before surgery and 24 h after surgery using the Quality of Recovery 40 questionnaire (QoR-40). Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), postoperative pain intensity, duration of post anesthesia care unit (PACU) stay and patient's satisfaction. RESULTS: Global QoR-40 score at 24 h after surgery was higher in the TEAS group (median [interquartile range], 183 [172-190]) compared with the control group (168 [154-183]) (P < 0.001). Compared with the control group, postoperative pain intensity and the cumulative number of opioids administered was lower in the TEAS group patients (P < 0.001). TEAS reduced the incidence of PONV and dizziness (P = 0.001), as well as the duration of PACU stay (P < 0.001). Simultaneously, the patient's satisfaction scores were higher in the TEAS group (P = 0.002). CONCLUSION: Preoperative TEAS enhances the quality of recovery, postoperative analgesia and patient's satisfaction, alleviates postoperative side effects and accelerates discharge after general anesthesia for thyroidectomy.

10.
Int J Clin Exp Med ; 8(4): 5781-7, 2015.
Article in English | MEDLINE | ID: mdl-26131165

ABSTRACT

BACKGROUND: In this prospective, randomized, double-blind study, we verified the hypothesis that TEAS can alleviate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. METHODS: 60 American Society of Anesthesiologists physical status (ASA) I-IIpatients, aged 18-60 year, scheduled for thyroidectomy were randomly allocated to TEAS or sham groups. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4) and Neiguan (PC6) before anesthesia. Anesthesia was maintained with sevoflurane adjusted to bispectral index (40-60) and target remifentanil 5.0 ng/ml. Mechanical pain thresholds were assessed using electronic von Frey. The primary outcome was mechanical pain thresholds. Secondary outcomes included postoperative pain scores, the time to first rescue analgesic, cumulative number of rescue analgesia, and side effects, including postoperative nausea and vomiting (PONV), dizziness and shivering in 24 h postoperatively. RESULTS: Baseline mechanical pain thresholds were similar between the groups. The analysis revealed the decrease in mechanical threshold was greater in the sham group than the TEAS group (P < 0.001). Postoperative pain scores and cumulative number of rescue analgesia were lower in the TEAS group (P < 0.05). In addition, TEAS group patients reduced the incidence of PONV and shivering. CONCLUSION: Preoperative TEAS can attenuate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy.

12.
Cardiovasc Drugs Ther ; 28(5): 425-32, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25022544

ABSTRACT

BACKGROUND: Anti-atherosclerotic effects of dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown in many studies. Since inflammation and immune response play a key role in atherogenesis, we examined the effect of DPP-4 inhibitors on the expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) Inflammasome and Interleukin-1beta (IL-1ß) in human macrophages. METHODS AND RESULTS: THP-1 macrophages were incubated with oxidized low density lipoprotein (ox-LDL) with or without DPP-4 inhibitors (sitagliptin and NVPDPP728). The effects of DPP-4 inhibitors on the expression of NLRP3, toll-like receptor 4 (TLR4) and pro-inflammatory cytokine IL-1ß were studied. Both DPP-4 inhibitors induced a significant reduction in NLRP3, TLR4 and IL-1ß expression; concurrently, there was an increase in glucagon like peptide 1 receptor (GLP-1R) expression. Simultaneously, DPP-4 inhibitors reduced phosphorylated-PKC, but not PKA, levels. To determine the role of PKC activation in the effects of DPP-4 inhibitors, cells were treated with PMA- which blocked the effect of DPP-4 inhibitors on NLRP3 and IL-1ß as well as TLR4 and GLP-1R. Over-expression of GLP-1R in macrophages with its agonist liraglutide also blocked the effects of PMA. CONCLUSION: DPP-4 inhibitors suppress NLRP3, TLR4 and IL-1ß in human macrophages through inhibition of PKC activity. This study provides novel insights into the mechanism of inhibition of inflammatory state and immune response in atherosclerosis by DPP-4 inhibitors.


Subject(s)
Carrier Proteins/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Inflammasomes/biosynthesis , Interleukin-1beta/biosynthesis , Macrophages/drug effects , Protein Kinase C/metabolism , Receptors, Glucagon/metabolism , Carrier Proteins/biosynthesis , Cell Culture Techniques , Cyclic AMP-Dependent Protein Kinases/biosynthesis , Gene Expression Regulation/drug effects , Glucagon-Like Peptide 1/analogs & derivatives , Glucagon-Like Peptide 1/pharmacology , Glucagon-Like Peptide-1 Receptor , Humans , Liraglutide , Macrophages/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Nitriles/antagonists & inhibitors , Nitriles/pharmacology , Phosphorylation/drug effects , Pyrazines/antagonists & inhibitors , Pyrazines/pharmacology , Pyrrolidines/antagonists & inhibitors , Pyrrolidines/pharmacology , Receptors, Glucagon/biosynthesis , Signal Transduction/drug effects , Sitagliptin Phosphate , Tetradecanoylphorbol Acetate/analogs & derivatives , Tetradecanoylphorbol Acetate/pharmacology , Toll-Like Receptor 4/biosynthesis , Triazoles/antagonists & inhibitors , Triazoles/pharmacology
13.
J Cardiovasc Pharmacol ; 64(1): 47-52, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24705175

ABSTRACT

Oxidized low-density lipoprotein (ox-LDL) uptake by monocytes/macrophages plays a pivotal role in atherogenesis. This study was designed to examine the effect of glucagon-like peptide-1 (GLP-1) agonists on ox-LDL uptake in macrophages. Human primary monocytes/macrophages were incubated with native GLP-1 (nGLP-1) or GLP-1 agonist liraglutide to evaluate their effect on ox-LDL uptake and the expression of scavenger receptors (SRs), such as SR-A, CD36, and lectin-like ox-LDL SR-1, in this process. Our study showed a decrease in ox-LDL uptake and CD36 expression in macrophages treated with nGLP-1 or liraglutide. However, nGLP-1 and liraglutide did not affect the expression of other SRs SR-A and lectin-like ox-LDL SR-1. Simultaneously, there was an increase in the expression of activated protein kinase A (PKA). To examine the role of PKA in the effects of nGLP-1 or liraglutide, we treated macrophages with PK inhibitor (6-22) amide, a PKA inhibitor, followed by treatment with nGLP-1 or liraglutide. Inhibition of PKA activation markedly reversed the effect of nGLP-1 or liraglutide on ox-LDL uptake and enhanced the expression of CD36. Our results suggest that GLP-1 agonism inhibits ox-LDL uptake through PKA/CD36 pathway in macrophages. This study provides a novel insight in the mechanism of foam cell formation and the role by GLP-1 agonists therein.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Glucagon-Like Peptide 1/analogs & derivatives , Glucagon-Like Peptide 1/agonists , Lipoproteins, LDL/metabolism , Atherosclerosis/pathology , CD36 Antigens/genetics , Cells, Cultured , Foam Cells/metabolism , Gene Expression Regulation/drug effects , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/pharmacology , Humans , Liraglutide , Macrophages/drug effects , Macrophages/metabolism , Monocytes/metabolism
14.
J Cardiovasc Pharmacol ; 63(2): 158-66, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24220312

ABSTRACT

BACKGROUND: Dyslipidemia, particularly increased LDL-cholesterol level in serum, is associated with atherosclerosis and fibrosis in different organs. This study was designed to investigate the effects of increase in LDL-cholesterol on renal fibrosis. METHODS: Wild-type (WT) and LDLr knockout (KO) mice were fed standard or high fat diet (HFD), and their kidneys were collected after 26 weeks of dietary intervention for identification of fibrosis and study of potential mechanisms. Additional studies were performed in cultured renal fibroblasts. RESULTS: We observed extensive and diffuse fibrosis in the kidneys of mice given HFD (P < 0.05 vs. standard chow). Fibrosis was associated with enhanced expression of fibronectin, nicotinamide adenine dinucleotide phosphate oxidases and activated p38 and p44/42 mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). There was evidence for accumulation of 4-hydroxynonenal, a lipid peroxidation product, in the kidneys and of ox-LDL in the arteries of LDLr KO mice given HFD. The expression of ox-LDL receptor LOX-1 and of transforming growth factor beta 1 (TGFß1) was increased in these kidneys. All these changes were more pronounced in LDLr KO mice than in the WT mice. In in vitro studies, treatment of fibroblasts from kidneys of LDLr KO mice with ox-LDL showed intense proliferation and collagen formation (all P < 0.05, fibroblasts from WT mice kidneys). Blockade of p38 MAPK, p44/42 MAPK, or NF-κB significantly attenuated expression of profibrotic signals, collagen formation, and proliferation of fibroblasts. CONCLUSIONS: HFD induces renal fibrosis in LDLr-null mice primarily through activation of the nicotinamide adenine dinucleotide phosphate oxidase MAPK-NF-κB pathway by ox-LDL.


Subject(s)
Diet, High-Fat/adverse effects , Kidney Diseases/etiology , Lipoproteins, LDL/metabolism , Receptors, LDL/genetics , Aldehydes/metabolism , Animals , Cell Proliferation , Cells, Cultured , Collagen/metabolism , Fibroblasts/pathology , Fibrosis , Kidney Diseases/pathology , Lipid Peroxidation , Male , Mice , Mice, Knockout , Mitogen-Activated Protein Kinases/metabolism , NADPH Oxidases/metabolism , NF-kappa B/metabolism , Transforming Growth Factor beta1/metabolism
15.
Acta Diabetol ; 51(3): 471-8, 2014.
Article in English | MEDLINE | ID: mdl-24363097

ABSTRACT

Studies show that dipeptidyl peptidase-4 (DPP-4) inhibitors may have an anti-atherosclerotic effect. Since foam cells are key components of atherosclerotic plaque, we studied the effect of DPP-4 inhibitors on foam cell formation. Foam cell formation was studied by treatment of THP-1 macrophages with oxidized low-density lipoprotein in the absence or presence of DPP-4 inhibitors (sitagliptin and NVPDPP728). The expression of scavenger receptors SRA, CD36 and LOX-1 was measured, and their role in foam cell formation in the presence of DPP-4 inhibitors was examined. In additional studies, role of protein kinase C and A in the effect of DPP-4 inhibitors was examined. Foam cell formation was markedly reduced by both DPP-4 inhibitors, as was the expression of CD36 and LOX-1 (CD36 â‰« LOX-1), but not SRA. Simultaneously, there was a reduction in phosphorylated PKC, but not PKA, content. Recovery of phosphorylated PKC following treatment of cells negated the effect of DPP-4 inhibitors on foam cell formation. Further, overexpression of CD36 or LOX-1 blocked the effect of DPP-4 inhibitors on foam cell formation. DPP-4 inhibitors repress foam cell formation through the inhibition of SRs CD36 and LOX-1, most likely via the inhibition of PKC activity. This study provides novel insights into the mechanism of inhibition of atherosclerosis by DPP-4 inhibitors.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Foam Cells/drug effects , Protein Kinase C/metabolism , Receptors, Scavenger/genetics , Atherosclerosis/drug therapy , Atherosclerosis/enzymology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Cell Line , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Down-Regulation/drug effects , Foam Cells/enzymology , Foam Cells/metabolism , Humans , Lipoproteins, LDL/metabolism , Macrophages/drug effects , Macrophages/enzymology , Macrophages/metabolism , Pyrazines/pharmacology , Receptors, Scavenger/metabolism , Sitagliptin Phosphate , Triazoles/pharmacology
16.
Acta Diabetol ; 50(6): 827-35, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23824323

ABSTRACT

Cardiovascular diseases are major killers in all developed societies and rapidly becoming the leading cause of morbidity and mortality in the developing world. Patients with diabetes mellitus are at particular risk of developing cardiovascular diseases. The present treatment options for management of diabetes have expanded since the development of glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. There is a growing body of evidence that these agents may have cardioprotective effects even in patients who do not have diabetes. Here, we discuss this evidence as well as pathways that DPP-4 inhibitors target in the cardiovascular system. These agents over time will find an appropriate place in the management of cardiovascular diseases.


Subject(s)
Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Animals , Cardiovascular Diseases/epidemiology , Cardiovascular System/drug effects , Diabetes Complications/prevention & control , Diabetes Mellitus/drug therapy , Glucagon-Like Peptide 1/antagonists & inhibitors , Glucagon-Like Peptide 1/physiology , Humans , Hypoglycemic Agents/therapeutic use
17.
Biochem Biophys Res Commun ; 437(1): 62-6, 2013 Jul 19.
Article in English | MEDLINE | ID: mdl-23806684

ABSTRACT

A growing body of evidence indicates that glucagon-like peptide-1 (GLP-1) agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors play an important role in modulating oxidant stress in vascular beds. However, the underlying mechanism of this process remains unclear. In recent studies, we observed an increase in GLP-1 receptor (GLP-1R) expression in the aorta of LOX-1 knock-out mice. Since LOX-1 is a pivotal regulator of reactive oxygen species (ROS), we conducted studies to identify relationship between LOX-1, ROS and GLP-1 agonism or DPP-4 antagonism. We observed a sustained decrease in GLP-1R expression in human vascular smooth muscle cells (VSMCs) treated with ox-LDL. When VSMCs were treated with different concentration of liraglutide (a GLP-1 agonist) or NVPDPP728 (a DPP-4 inhibitor), expression of ROS decreased compared with ox-LDL alone treatment. To further prove that LOX-1 plays a pivotal role in ROS and GLP-1R expression, we treated VSMCs with LOX-1 antibody or transfected cells with human LOX-1 cDNA. The inhibitory effect of ox-LDL on GLP-1R expression was reversed with anti-LOX-1 antibody treatment, while the inhibitory effect of liraglutide and NVPDPP728 on ROS generation was attenuated when cells were transfected with LOX-1 cDNA. Our results suggest that LOX-1 may play a bridging role in GLP-1 activation and ROS interaction.


Subject(s)
Mitochondria/metabolism , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/metabolism , Reactive Oxygen Species/metabolism , Receptors, Glucagon/metabolism , Scavenger Receptors, Class E/metabolism , Animals , Aorta/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Fluorescence , Gene Deletion , Glucagon-Like Peptide 1/analogs & derivatives , Glucagon-Like Peptide 1/pharmacology , Glucagon-Like Peptide-1 Receptor , Humans , Lipoproteins, LDL/pharmacology , Liraglutide , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/drug effects , Myocytes, Smooth Muscle/drug effects
18.
Biochem Biophys Res Commun ; 374(3): 485-9, 2008 Sep 26.
Article in English | MEDLINE | ID: mdl-18640095

ABSTRACT

This is the first report of a poly-3-hydroxybutyrate (PHB) synthase in Escherichia coli. The enzyme was isolated from the periplasm using ammonium sulfate fractionation, hydrophobic, and size-exclusion chromatography and identified by LC/MS/MS as YdcS, a component of a putative ABC transporter. Green Fluorescent Protein-tagged ydcS, purified by 2D native gel electrophoresis, also exhibited PHB synthase activity. Optimal conditions for enzyme activity were 37 degrees C, pH 6.8-7.5, 100 mM KCl. K(m) was 0.14 mM and V(max) was 18.7 nmol/mg protein/min. The periplasms of deletion mutants displayed <25% of the activity of the parent strain. Deletion mutants exhibited approximately 25% less growth in M9 medium, glucose, and contained approximately 30% less PHB complexed to proteins (cPHB) in the outer membranes, but the same concentration of chloroform-extractable PHB as wild-type cells. The primary sequence of YdcS suggests it may belong to the alpha-/beta-hydrolase superfamily which includes polyhydroxybutyrate (PHB) synthases, lipases, and esterases.


Subject(s)
Acyltransferases/metabolism , Escherichia coli Proteins/metabolism , Escherichia coli/enzymology , Periplasm/enzymology , Acyltransferases/genetics , Acyltransferases/isolation & purification , Amino Acid Sequence , Chloroform/chemistry , Escherichia coli/genetics , Escherichia coli/growth & development , Escherichia coli Proteins/genetics , Escherichia coli Proteins/isolation & purification , Gene Deletion , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/isolation & purification , Green Fluorescent Proteins/metabolism , Molecular Sequence Data , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Solubility
19.
Biochem Biophys Res Commun ; 312(2): 351-4, 2003 Dec 12.
Article in English | MEDLINE | ID: mdl-14637144

ABSTRACT

The interaction of poly(allylamine hydrochloride) (PAH) with TAR RNA has been studied by quartz crystal microbalance (QCM) cooperating with capillary electrophoresis (CE). Experimental results showed that PAH had high affinity for TAR RNA. In particular, PAH could disrupt the interaction of Tat peptide with TAR RNA, which is critical for HIV-1 virus replication. The approaches described here indicate that they are powerful for studying the binding processes of Tat peptide-TAR RNA and drug-TAR RNA, having great significance for the design of new drug.


Subject(s)
Biosensing Techniques/methods , Electrophoresis, Capillary/methods , Gene Products, tat/chemistry , HIV-1/chemistry , Polyamines/chemistry , RNA, Viral/chemistry , RNA-Binding Proteins/chemistry , Biosensing Techniques/instrumentation , HIV-1/genetics , Humans , Protein Binding/drug effects , Quantitative Structure-Activity Relationship , RNA, Viral/genetics , RNA-Binding Proteins/genetics , tat Gene Products, Human Immunodeficiency Virus
20.
Electrophoresis ; 24(18): 3219-23, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14518048

ABSTRACT

Sharp peaks of Escherichia coli JM 109 (up to 1 300 000 theoretical plates) were recorded with either extremely diluted (< 5 mM) or extremely concentrated (ca. 150 mM) Tris-borate (TB) running buffers. However, under the conditions of yielding sharp peaks, migration time of E. coli was irreproducible. Critial factors influencing reproducibility were found to include bacterial growth phase, storage condition, cell pretreatment before injection, and concentration of running buffer. Buffer concentrations in the range of 20-100 mM TB were essential for reproducibility. E. coli JM 109 was shown to be sensitive to ultrasonification. Bacterial growth and storage conditions could be monitored by CE, with results comparable to those obtained with optical methods.


Subject(s)
Electrophoresis, Capillary/methods , Escherichia coli/isolation & purification , Bacteriological Techniques/instrumentation , Borates/chemistry , Buffers , Electrophoresis, Capillary/instrumentation , Escherichia coli/growth & development , Hydrogen-Ion Concentration , Reproducibility of Results , Time Factors , Ultrasonics
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