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ApoE transcription

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
Sara Ibrahim Omar, Marco Gaetano Lepre, Umberto Morbiducci, Marco Agostino Deriu, Jack A Tuszynski
TP53 is the most mutated gene in all cancers. The mutant protein also accumulates in cells. The high frequency of p53 mutations makes the protein a promising target for anti-cancer therapy. Only a few molecules have been found, using in vitro screening, to reactivate the mutant protein. APR-246 is currently the most successful mutant p53 activator, which reactivates the transcriptional activity of p53 by covalently binding to C124 of the protein. We have recently created in silico models of G245S-mp53 in its apo and DNA-bound forms...
2018: PloS One
Young Woo Park, Young Yoon Jang, Hyun Kyu Joo, Jae Young Lee
The cellular redox state of organisms continues to fluctuate during the metabolism. All organisms have various sensors that help detect and adapt to changes in the redox state. Nicotinamide adenine dinucleotides (NAD+ /NADH), which are involved in various cellular metabolic activities as cofactors, have been revealed as the key molecules sensing the intra-cellular redox state. The Rex family members are well conserved transcriptional repressors that regulate the expression of respiratory genes by sensing the redox state according to the intra-cellular NAD+ /NADH balance...
September 5, 2018: Scientific Reports
Giedrius Sasnauskas, Elena Manakova, Kęstutis Lapėnas, Kotryna Kauneckaitė, Virginijus Siksnys
B3 transcription factors constitute a large plant-specific protein superfamily, which plays a central role in plant life. Family members are characterized by the presence of B3 DNA-binding domains (DBDs). To date, only a few B3 DBDs were structurally characterized; therefore, the DNA recognition mechanism of other family members remains to be elucidated. Here, we analyze DNA recognition mechanism of two structurally uncharacterized B3 transcription factors, ABI3 and NGA1. Guided by the structure of the DNA-bound B3 domain of Arabidopsis transcriptional repressor VAL1, we have performed mutational analysis of the ABI3 B3 domain...
September 5, 2018: FEBS Journal
Ángela VinuÉ, Sergio MartÍnez-HervÁs, Andrea Herrero-Cervera, Verónica SÁnchez-GarcÍa, Irene AndrÉs-Blasco, Laura Piqueras, MarÍa JesÚs Sanz, JosÉ TomÁs Real, Juan F Ascaso, Deborah Jane Burks, Herminia GonzÁlez-Navarro
Previous studies indicate a role of CDKN2A/2B/2BAS genes in atherosclerosis and type 2 diabetes mellitus (T2DM). Progression of these diseases is accompanied by T-cell imbalance and chronic inflammation. Our main objective was to investigate a potential association between CDKN2A/2B/2BAS gene expression and T cell phenotype in T2DM and coronary artery disease (CAD) in humans, and to explore the therapeutic potential of these genes to restore immune cell homeostasis and disease progression. Reduced mRNA levels of CDKN2A (p16Ink4a ), CDKN2B (p15Ink4b ), and CDKN2BAS were observed in human T2DM and T2DM-CAD subjects compared with controls...
August 15, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Joshua C Bis, Xueqiu Jian, Brian W Kunkle, Yuning Chen, Kara L Hamilton-Nelson, William S Bush, William J Salerno, Daniel Lancour, Yiyi Ma, Alan E Renton, Edoardo Marcora, John J Farrell, Yi Zhao, Liming Qu, Shahzad Ahmad, Najaf Amin, Philippe Amouyel, Gary W Beecham, Jennifer E Below, Dominique Campion, Camille Charbonnier, Jaeyoon Chung, Paul K Crane, Carlos Cruchaga, L Adrienne Cupples, Jean-François Dartigues, Stéphanie Debette, Jean-François Deleuze, Lucinda Fulton, Stacey B Gabriel, Emmanuelle Genin, Richard A Gibbs, Alison Goate, Benjamin Grenier-Boley, Namrata Gupta, Jonathan L Haines, Aki S Havulinna, Seppo Helisalmi, Mikko Hiltunen, Daniel P Howrigan, M Arfan Ikram, Jaakko Kaprio, Jan Konrad, Amanda Kuzma, Eric S Lander, Mark Lathrop, Terho Lehtimäki, Honghuang Lin, Kari Mattila, Richard Mayeux, Donna M Muzny, Waleed Nasser, Benjamin Neale, Kwangsik Nho, Gaël Nicolas, Devanshi Patel, Margaret A Pericak-Vance, Markus Perola, Bruce M Psaty, Olivier Quenez, Farid Rajabli, Richard Redon, Christiane Reitz, Anne M Remes, Veikko Salomaa, Chloe Sarnowski, Helena Schmidt, Michael Schmidt, Reinhold Schmidt, Hilkka Soininen, Timothy A Thornton, Giuseppe Tosto, Christophe Tzourio, Sven J van der Lee, Cornelia M van Duijn, Badri Vardarajan, Weixin Wang, Ellen Wijsman, Richard K Wilson, Daniela Witten, Kim C Worley, Xiaoling Zhang, Celine Bellenguez, Jean-Charles Lambert, Mitja I Kurki, Aarno Palotie, Mark Daly, Eric Boerwinkle, Kathryn L Lunetta, Anita L Destefano, Josée Dupuis, Eden R Martin, Gerard D Schellenberg, Sudha Seshadri, Adam C Naj, Myriam Fornage, Lindsay A Farrer
The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants...
August 14, 2018: Molecular Psychiatry
Martina Gast, Bernhard H Rauch, Shinichi Nakagawa, Arash Haghikia, Andrzej Jasina, Jan Haas, Neetika Nath, Lars Jensen, Andrea Stroux, Andreas Böhm, Julian Friebel, Ursula Rauch, Carsten Skurk, Stefan Blankenberg, Tanja Zeller, Kannanganattu V Prasanth, Benjamin Meder, Andreas Kuss, Ulf Landmesser, Wolfgang Poller
Background: The immune system is considered a key driver of atherosclerosis, and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) are implicated in immune control. We previously described that lncRNA MALAT1 is involved in cardiac innate immunity in a myocarditis model. Here, we investigated the impact of MALAT1 deficiency upon atherosclerosis development. Methods and Results: Heterozygous MALAT1-deficient ApoE-/- mice displayed massive immune system dysregulation and atherosclerosis within two months even when kept on normal diet...
August 8, 2018: Cardiovascular Research
Samia Neggazi, Laurence Canaple, Nadjiba Hamlat, Karine Gauthier, Jacques Samarut, Giampiero Bricca, Souhila Aouichat-Bouguerra, Michel Beylot
Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE-/- mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE-/- mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver...
2018: Journal of Vascular Research
Rou-Ling Cho, Chien-Chung Yang, Hui-Ching Tseng, Li-Der Hsiao, Chih-Chung Lin, Chuen-Mao Yang
BACKGROUND AND PURPOSE: Haem oxygenase-1 (HO-1) is induced by thiazolidinediones including rosiglitazone and exerts anti-inflammatory effects in various models. However, the molecular mechanisms underlying rosiglitazone-induced HO-1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). EXPERIMENTAL APPROACH: HO-1 expression was determined by real time-PCR, Western blotting and promoter reporter analyses. Signalling pathways were investigated using pharmacological inhibitors or specific siRNAs...
October 2018: British Journal of Pharmacology
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