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ApoE transcription

Yi Yan, Fei He, Zhonghao Li, Ruoting Xu, Ting Li, Jinyu Su, Xianyan Liu, Ming Zhao, Wei Wu
BACKGROUND AND AIMS: It has been well established that ezetimibe blocks cholesterol absorption to prevent the negative effects of a high-fat diet in atherosclerosis. However, the exact mechanism is unknown. Here we use a transgenic zebrafish, which expresses different fluorescent proteins on either endothelial cells or granulocytes and macrophages, to explore the specific mechanism of ezetimibe and its role in reducing atherosclerosis-related hypercholesteremia. METHODS: Zebrafish larvae were exposed to a control diet, high cholesterol diet (HCD) or a HCD with ezetimibe treatment...
November 16, 2018: Atherosclerosis
Diana Cortes-Selva, Andrew F Elvington, Andrew Ready, Bartek Rajwa, Edward J Pearce, Gwendalyn J Randolph, Keke C Fairfax
Hepatic macrophages play an essential role in the granulomatous response to infection with the parasitic helminth Schistosoma mansoni , but the transcriptional changes that underlie this effect are poorly understood. To explore this, we sorted the two previously recognized hepatic macrophage populations (perivascular and Kupffer cells) from naïve and S. mansoni -infected male mice and performed microarray analysis as part of the Immunological Genome Project. The two hepatic macrophage populations exhibited remarkably different genomic profiles...
2018: Frontiers in Immunology
Wenzhang Wang, Xiongwei Zhu
ε4 allele of ApoE is the strongest genetic risk factor for late onset Alzheimer's disease (AD). Supplementation of ApoE proteins or mimetics has been pursued for drug developments against AD. A very low-density lipoprotein (HDL) mimetic peptide 4F was shown to alleviate AD-related deficits in APP transgenic mice, and this editorial highlights a study by Chernick et al. who use both mouse and human neuroglial cells to explore the mechanism underlying beneficial effects of this peptide. The authors demonstrate that 4F peptide significantly increased the secretion and lipidation of ApoE in the absence and presence of Aβ independent of de novo transcription/translation, but requiring ABCA1 and the integrity of the secretory pathway between ER and Golgi...
November 26, 2018: Journal of Neurochemistry
Houguo Xu, Zhangbin Liao, Chengqiang Wang, Yuliang Wei, Mengqing Liang
To investigate the different effects of dietary α-linolenic acid (ALA) and linoleic acid (LA) on the euryhaline fish Japanese seabass, a feeding trial followed by hepatic transcriptome assay was conducted. Two experimental diets containing 10% LA-rich sunflower seed oil (diet LA) or 10% ALA-rich perilla oil (diet ALA) were used in the feeding trial. LA and ALA in diets were characteristically incorporated into fish tissues while no significant difference was observed in growth performance and body proximate composition between groups LA and ALA...
November 7, 2018: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Bernd T Hermann, Sven Wuertz, Klaus H Vanselow, Carsten Schulz, Kevin T Stiller
Elevated concentrations of carbon dioxide are a common stressor for fish and other aquatic animals. In particular, intensive aquaculture can impose prolonged periods of severe environmental hypercapnia, manifold exceeding CO2 concentrations of natural habitats. In order to cope with this stressor, gills are essential and constitute the primary organ in the acclimatization process. Yet, despite a general understanding of changes in ion regulation, not much is known with regard to other cellular mechanisms. In this study, we apply RT-qPCR to investigate changes in the expression of several genes associated with metabolism, stress and immunity within gills of juvenile turbot (Psetta maxima) after an eight-week exposure to different concentrations of CO2 (low = ∼3000 μatm, medium = ∼15,000 μatm and high = ∼25,000 μatm CO2 )...
November 3, 2018: Aquatic Toxicology
Sheng-Chao Ma, Guan-Jun Lu, Hui Zhang, Ning Ding, Yan-Hua Wang, Xiao-Ling Yang, An-Ning Yang, Hui-Ping Zhang, Yi-Deng Jiang
The effect of homocysteine (Hcy) on extracellular‑superoxide dismutase (EC‑SOD) methylation levels in the aorta of mice was observed and the underlying mechanism of THP‑1 monocyte‑derived macrophages was investigated. The key targets of Hcy‑induced EC‑SOD methylation changes were identified. ApoE‑/‑ mice were fed different diets for 15 weeks and the concentrations of Hcy and lipids were subsequently detected using an automatic biochemistry analyzer. Serum levels of Hcy and lipids were significantly higher in the Meth group compared with the control group...
November 15, 2018: International Journal of Molecular Medicine
Lipei Liu, Peng Zeng, Xiaoxiao Yang, Yajun Duan, Wenwen Zhang, Chuanrui Ma, Xiaomeng Zhang, Shu Yang, Xiaoju Li, Jie Yang, Yu Liang, Hao Han, Yan Zhu, Jihong Han, Yuanli Chen
Objective- Vascular calcification is a major risk factor for rupture of atherosclerotic plaques. High expression of BMP2 (bone morphogenetic protein 2) in lesions suggests its importance in vascular calcification during atherosclerosis. Teniposide is a Topo II (DNA topoisomerase II) inhibitor and is used for cancer treatment. Previously, we reported that teniposide activated macrophage ABCA1 (ATP-binding cassette transporter A1) expression and free cholesterol efflux indicating Topo II inhibitors may demonstrate antiatherogenic properties...
October 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Júlia Canet-Pons, Ralf Schubert, Ruth Pia Duecker, Roland Schrewe, Sandra Wölke, Matthias Kieslich, Martina Schnölzer, Andreas Chiocchetti, Georg Auburger, Stefan Zielen, Uwe Warnken
Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Employing global proteomic profiling of cerebrospinal fluid from patients at ages around 15 years, we detected reduced calbindin, reelin, cerebellin-1, cerebellin-3, protocadherin fat 2, sempahorin 7A, and increased apolipoprotein B and J peptides...
October 21, 2018: Neurogenetics
Yun Zhao, Lu Yan, Lu Peng, XueFeng Huang, GuiXiang Zhang, BingQian Chen, Jie Ren, Yu Zhou, LiChao Yang, Li Peng, Xin Jin, YiQing Wang
BACKGROUND: Atherosclerosis is the main underlying cause of most cardiovascular diseases, and monocyte migrating to the vascular wall and subsequently differentiating into macrophage are critical steps in the process of atherosclerosis. The goal of this study was to clarify the effect of oleoylethanolamide (OEA) on monocyte migration and subsequent macrophage formation in the vascular wall. METHODS: We studied OEA in two monocyte-migrating systems in vitro: one was a single cell system whereby monocytes were exposed to OEA directly; the other was a co-culture system whereby monocytes were exposed to OEA-treated macrophages...
June 23, 2018: Pharmacological Reports: PR
Hongxuan Li, Jingyuan Li, Xiuxin Jiang, Shangming Liu, Yan Liu, Weiqian Chen, Jianmin Yang, Cheng Zhang, Wencheng Zhang
OBJECTIVE: Melatonin, an endogenous neurohormone secreted predominately by the pineal gland, has a variety of physiological functions. However, its protective role in atherosclerosis is not clear. In this study, we sought to investigate the potential effects of melatonin in modulating atherosclerotic plaque stability in apolipoprotein E knockout (ApoE) mice. METHOD AND RESULTS: Smooth muscle cells were treated with melatonin, which significantly increased mRNA and protein levels of a key intracellular enzyme essential for collagen maturation and secretion, prolyl-4-hydroxylase α1 (P4Hα1)...
October 17, 2018: Journal of Hypertension
Yuan Zhou, Qian Wang, Qi Yang, Jielin Tang, Chonghui Xu, Dongwei Gai, Xinwen Chen, Jizheng Chen
Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV) replication in Huh7 human liver cells and in a mouse model of HCV infection. Viral replication was markedly suppressed by the HDAC3 inhibitor at concentrations below 1 mmol/L, with no cellular toxicity. This was accompanied by upregulation of liver-expressed antimicrobial peptide 1(LEAP-1) and downregulation of apolipoprotein-A1 (Apo-A1), as determined by microarray and quantitative RT-PCR analyses...
October 17, 2018: Virologica Sinica
Changan Liu, Jacqueline Chyr, Weiling Zhao, Yungang Xu, Zhiwei Ji, Hua Tan, Claudio Soto, Xiaobo Zhou
Alzheimer's disease (AD) is the most common cause of dementia. Although genome-wide association study (GWAS) have reported hundreds of single-nucleotide polymorphisms (SNPs) and genes linked to AD, the mechanisms about how these SNPs modulate the development of AD remain largely unknown. In this study, we performed GWAS for three traits in cerebrospinal fluid (CSF) and one clinical trait in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Our analysis identified five most significant AD related SNPs (FDR < 0...
2018: Frontiers in Genetics
Ahmed I Mahmoud, Francisco X Galdos, Katherine A Dinan, Mark P Jedrychowski, Jeffrey C Davis, Ana Vujic, Inbal Rachmin, Christian Shigley, James R Pancoast, Samuel Lee, Jennifer Hollister-Lock, Catherine M MacGillivray, Steven P Gygi, Douglas A Melton, Gordon C Weir, Richard T Lee
The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of the in vivo microenvironment may be mimicked by providing specific cues to cultured cells. Here, we show that after isolation and during maintenance in culture, adherent rat islets reduce expression of key β-cell transcription factors necessary for β-cell function and that soluble pancreatic decellularized matrix (DCM) can enhance β-cell gene expression...
2018: PloS One
Marcela Fuentes, Nicolás Santander, Víctor Cortés
The actions of insulin on intestinal cholesterol absorption and lipoprotein secretion are not well understood. Herein, we determined the effects of insulin on the levels of cholesterol transporter scavenger receptor, class B, type I (SR-BI), cellular cholesterol uptake, intracellular lipid accumulation, and lipoprotein secretion in a cellular model of human intestinal epithelium. METHODS: CaCo-2 cells were cultured to postconfluency in Transwell filters and stimulated with glucose (25 mM) in the presence or absence of insulin (100 nM) at their basolateral surface...
October 2, 2018: Journal of Cellular Biochemistry
Meera Kumari, Ravi Kant Pal, Alok K Mishra, Sarita Tripathi, Bichitra Kumar Biswal, Kishore K Srivastava, Ashish Arora
Rv3488 of Mycobacterium tuberculosis H37Rv has been assigned to the phenolic acid decarboxylase repressor (PadR) family of transcriptional regulators that play key roles in multi-drug resistance and virulence of prokaryotes. The binding of cadmium, zinc, and several other metals to Rv3488 was discovered and characterized by ITC to be an exothermic process. Crystal structures of apo-Rv3488 and Rv3488 in complex with cadmium or zinc ions were determined by X-ray crystallography. Structure of Rv3488 revealed a dimeric protein with N-terminal winged-helix-turn-helix DNA-binding domains composed of helices α1, α2, α3, strand β1 and β2, with the dimerization interface being formed of helices α4 and α1...
September 28, 2018: Biochemical Journal
Jinli Chen, Fei Shang, Lulu Wang, Linhai Zou, Tingting Bu, Liming Jin, Yuesheng Dong, Nam-Chul Ha, Chunshan Quan, Ki Hyun Nam, Yongbin Xu
Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator that positively regulates the transcription of the first two enzymes of the TCA cycle, namely, citZ and citB, by sensing accumulated intracellular citrate. CcpE comprises an N-terminal DNA-binding domain and a C-terminal regulatory domain (RD) and senses citrate with conserved arginine residues in the RD. Although the crystal structure of the apo SaCcpE-RD has been reported, the citrate-responsive and DNA-binding mechanisms by which CcpE regulates TCA activity remain unclear...
October 3, 2018: Biochemistry
Gavin Morris, Naadira Pahad, Heini W Dirr, Sylvia Fanucchi
FOXP2 is a transcriptional repressor involved in development of the human brain and is the first gene product to be linked to the evolution of human speech. FOXP2 belongs to the FOX superfamily of proteins that share a common winged helix DNA binding domain - the forkhead domain. A divalent cation (Mg2+ or Ca2+ ) has been identified bound to a group of highly conserved residues in a number of FOX forkhead domain crystal structures. This work aims to investigate the role of the conserved divalent cation binding site by studying both the structure and DNA-binding function of the FOXP2 forkhead domain when in the presence and absence of either cation (Mg2+ or Ca2+ )...
September 15, 2018: Archives of Biochemistry and Biophysics
Cheng Wang, Wenjing Xu, Minglu Liang, Dan Huang, Kai Huang
C1q/tumor necrosis factor-related protein 13 (CTRP13) is a secreted adipokine that can ameliorate abnormal glucose and lipid metabolism. However, the functional role of CTRP13 in the development of atherosclerotic plaques has yet to be described. In this study, we collected blood samples from patients of coronary artery diseases and apolipoprotein E (ApoE)-/- mice that were fed a Western diet for 12 wk to induce atherosclerosis and found that serum CTRP13 level was decreased. En face staining of aortas and aortic sinus in ApoE-/- mice showed that ectopic CTRP13 infusion in vivo dramatically decreased lesion areas, as well as reduced inflammatory responses with less macrophage content...
September 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Elisa A Liehn, Victor Ponomariov, Rodica Diaconu, Ioana Streata, Mihai Ioana, Gustavo E Crespo-Avilan, Sauri Hernández-Reséndiz, Hector A Cabrera-Fuentes
The presence of different APOE isoforms represents a well-known risk factor for cardiovascular diseases. Besides the pleiotropic effects of APOE polymorphism on heart and neurological diseases, this review summarizes the less-known functions of APOE and the possible implications for cardiovascular disorders. Beyond the role as lipid transporting protein, its involvement in lipid membrane homeostasis and signaling, as well as its nuclear transcriptional effects suggests a more complex role of APOE, receiving great interest from researchers and physicians from all medical fields...
September 10, 2018: Archives of Medical Research
Mark W Logue, Daniel Lancour, John Farrell, Irina Simkina, M Daniele Fallin, Kathryn L Lunetta, Lindsay A Farrer
The genetic architecture of late-onset Alzheimer disease (AD) in African Americans (AAs) differs from that in persons of European ancestry. In addition to APOE , genome-wide association studies (GWASs) of AD in AA samples have implicated ABCA7 , COBL , and SLC10A2 as AA-AD risk genes. Previously, we identified by whole exome sequencing a small number of AA AD cases and subsequent genotyping in a large AA sample of AD cases and controls association of AD risk with a pair of rare missense variants in AKAP9 . In this study, we performed targeted deep sequencing (including both introns and exons) of approximately 100 genes previously linked to AD or AD-related traits in an AA cohort of 489 AD cases and 472 controls to find novel AD risk variants...
2018: Frontiers in Neuroscience
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