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ApoE transcription

Lijie Ren, Lei Wang, Tao You, Yifei Liu, Fan Wu, Li Zhu, Chaojun Tang
OBJECTIVE: Emerging evidence shows that perivascular adipose tissue (PVAT) is crucially involved in inflammation and cardiovascular diseases. However, controversial results have been reported regarding the effect of PVAT in atherosclerosis. This study aimed to determine the role of PVAT in disturbed blood flow (d-flow)-induced carotid plaque formation. METHODS: ApoE-/- male mice underwent partial carotid ligation (PCL) to induce d-flow in the left carotid artery (LCA) and were fed a high-fat diet for 2 weeks...
February 15, 2019: Journal of Vascular Surgery
Menno Hoekstra, Joya E Nahon, Laura M de Jong, Mara J Kröner, Lidewij R de Leeuw, Miranda Van Eck
The nuclear receptor liver X receptor (LXR) impacts on cholesterol metabolism as well as hepatic lipogenesis via transcriptional regulation. It is proposed that inhibition of the protein arginine methyltransferase 3 (PRMT3) uncouples these two transcriptional pathways in vivo by acting as a specific lipogenic coactivator of LXR. Here we validated the hypothesis that treatment with the allosteric PRMT3 inhibitor SGC707 will diminish the hepatic steatosis extent, while leaving global cholesterol metabolism, important in cholesterol-driven pathologies like atherosclerosis, untouched...
February 15, 2019: Biochimica et biophysica acta. Molecular basis of disease
Alejandro R Roda, Laia Montoliu-Gaya, Sandra Villegas
Alzheimer's disease (AD), the most common type of dementia worldwide, is characterized by high levels of amyloid-β (Aβ) peptide and hyperphosphorylated tau protein. Genetically, the ɛ4 allele of apolipoprotein E (ApoE) has been established as the major risk factor for developing late-onset AD (LOAD), the most common form of the disease. Although the role ApoE plays in AD is still not completely understood, a differential role of its isoforms has long been known. The current review compiles the involvement of ApoE isoforms in amyloid-β protein precursor transcription, Aβ aggregation and clearance, synaptic plasticity, neuroinflammation, lipid metabolism, mitochondrial function, and tau hyperphosphorylation...
February 11, 2019: Journal of Alzheimer's Disease: JAD
Minsik Park, Seunghwan Choi, Suji Kim, Joohwan Kim, Dong-Keon Lee, Wonjin Park, Taesam Kim, Jiwon Jung, Jong Yun Hwang, Moo-Ho Won, Sungwoo Ryoo, Seung Goo Kang, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Vascular smooth muscle cells (VSMCs) play an important role in maintaining vascular function. Inflammation-mediated VSMC dysfunction leads to atherosclerotic intimal hyperplasia and preeclamptic hypertension; however, the underlying mechanisms are not clearly understood. We analyzed the expression levels of microRNA-155 (miR-155) in cultured VSMCs, mouse vessels, and clinical specimens and then assessed its role in VSMC function. Treatment with tumor necrosis factor-α (TNF-α) elevated miR-155 biogenesis in cultured VSMCs and vessel segments, which was prevented by NF-κB inhibition...
February 15, 2019: Experimental & Molecular Medicine
Hua Tian, Yanyan Li, Panpan Kang, Zhichao Wang, Feng Yue, Peng Jiao, Nana Yang, Shucun Qin, Shutong Yao
This study was designed to explore the inductive effect of glycated high-density lipoprotein (gly-HDL) on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its relationship with autophagy. Our results showed that gly-HDL caused macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α, and CHOP up-regulation, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and the gene silencing of PERK and CHOP...
February 12, 2019: Journal of Cellular and Molecular Medicine
Francisca Gallego Del Sol, José R Penadés, Alberto Marina
Bacillus phages use a communication system, termed "arbitrium," to coordinate lysis-lysogeny decisions. Arbitrium communication is mediated by the production and secretion of a hexapeptide (AimP) during lytic cycle. Once internalized, AimP reduces the expression of the negative regulator of lysogeny, AimX, by binding to the transcription factor, AimR, promoting lysogeny. We have elucidated the crystal structures of AimR from the Bacillus subtilis SPbeta phage in its apo form, bound to its DNA operator and in complex with AimP...
February 6, 2019: Molecular Cell
Lorena Novoa-Aponte, David Ramírez, José M Argüello
Copper homeostasis in pathogenic bacteria is critical for cuproprotein assembly and virulence. However, in vivo biochemical analyses of these processes are challenging, which has prevented defining and quantifying the homeostatic interplay between Cu+ -sensing transcriptional regulators, chaperones, and sequestering molecules. The cytoplasm of Pseudomonas aeruginosa contains a Cu+ -sensing transcriptional regulator, CueR, and two homologous metal chaperones, CopZ1 and CopZ2, forming a unique system for studying Cu+ homeostasis...
February 4, 2019: Journal of Biological Chemistry
Runze Qiu, Jun Long, Liyu Zhou, Yuanjing Ma, Lingang Zhao, Fumin Liu, Dongping Yuan
Atherosclerosis (AS) is a complicated arterial disease resulting from abnormal lipid deposition and inflammatory injury, which is attributed to Yin deficiency, accumulation of heat materials, and stasis of blood flow in Traditional Chinese Medicine (TCM) theory. Thus, according to TCM theory, the method of nourishing Yin (Yangyin), clearing away heat (Qingre), and promoting blood circulation (Huoxue) is a reasonable strategy, which has achieved remarkable clinical efficacy in the treatment of AS, but the mechanisms remain to be known...
2019: Evidence-based Complementary and Alternative Medicine: ECAM
Jérôme Eberhardt, Alastair G McEwen, William Bourguet, Dino Moras, Annick Dejaegere
The retinoic X receptor (RXR) plays a crucial role in the superfamily of nuclear receptors (NRs) by acting as an obligatory partner of several nuclear receptors; its role as a transcription factor is thus critical in many signalling pathways, such as metabolism, cell development, differentiation and cellular death. The first published structure of the apo ligand-binding domain (LBD) of RXRα, which is still used as a reference today, contained inaccuracies. In the present work, these inaccuracies were corrected using modern crystallographic tools...
February 1, 2019: Acta Crystallographica. Section F, Structural Biology Communications
Baptiste Rode, Nadira Y Yuldasheva, Paul D Baxter, Alicia Sedo, Justin F Ainscough, Michael Shires, Mark T Kearney, Marc A Bailey, Stephen B Wheatcroft, David J Beech
Transient Receptor Potential Canonical 5 (TRPC5) is a subunit of a Ca2+ -permeable non-selective cationic channel which negatively regulates adiponectin but not leptin in mice fed chow diet. Adiponectin is a major anti-inflammatory mediator and so we hypothesized an effect of TRPC5 on the inflammatory condition of atherosclerosis. Atherosclerosis was studied in aorta of ApoE-/- mice fed western-style diet. Inhibition of TRPC5 ion permeation was achieved by conditional transgenic expression of a dominant negative ion pore mutant of TRPC5 (DNT5)...
January 28, 2019: Scientific Reports
Jung Hwan Yoon, Yeon Soo Lee, Olga Kim, Hassan Ashktorab, Duane T Smoot, Suk Woo Nam, Won Sang Park
BACKGROUND: Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis. Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β (Aβ) production...
January 21, 2019: World Journal of Gastroenterology: WJG
Daniel W Sirkis, Luke W Bonham, Celeste M Karch, Jennifer S Yokoyama
PURPOSE OF REVIEW: Over the last year, research into the immunological and inflammatory signatures of frontotemporal lobar degeneration (FTLD) has accelerated greatly. Herein, we highlight recently proposed roles of brain-resident microglia as well as peripheral myeloid cells in frontotemporal dementia (FTD)-spectrum disorders. RECENT FINDINGS: Recent unbiased genetic, transcriptomic, and proteomic surveys using human data confirm significantly altered immune-function genes as well as transcript and protein modules associated with inflammatory and immune function...
January 21, 2019: Current Opinion in Neurology
Fang-da Li, Hao Nie, Cui Tian, Hong-Xia Wang, Bao-Hua Sun, Hua-Liang Ren, Xu Zhang, Peng-Zhi Liao, Duan Liu, Hui-Hua Li, Yue-Hong Zheng
Low-molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice...
January 14, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Ronald E Rondon, Corey J Wilson
The lactose repressor, LacI (I+ YQR ) is an archetypal transcription factor that has been a workhorse in many synthetic genetic networks. LacI represses gene expression (apo ligand) and is induced upon binding of the ligand isopropyl β-D-1-thiogalactopyranoside (IPTG). Recently, laboratory evolution was used to confer inverted function in the native LacI topology resulting in anti-LacI (antilac) function (IA YQR ), where IPTG binding results in gene suppression. Here we engineered 46 antilacs with alternate DNA binding function (IA ADR )...
January 2, 2019: ACS Synthetic Biology
Rahul Patil, Biswaranjan Mohanty, Bonan Liu, Indu R Chandrashekaran, Stephen J Headey, Martin L Williams, Craig S Clements, Olga Ilyichova, Bradley C Doak, Patrick Genissel, Richard J Weaver, Laurent Vuillard, Michelle L Halls, Christopher J H Porter, Martin J Scanlon
Peroxisome proliferator-activated receptor α (PPARα) is a transcriptional regulator of lipid metabolism. GW7647 is a potent PPARα agonist that must reach the nucleus to activate this receptor. In cells expressing human fatty acid-binding protein 1 (FABP1), GW7647 treatment increases FABP1's nuclear localization, and potentiates GW7647-mediated PPARα activation; GW7647 is less effective in cells that do not express FABP1. To elucidate the underlying mechanism, here we substituted residues in FABP1 known to dictate lipid signaling by other intracellular lipid-binding proteins...
December 31, 2018: Journal of Biological Chemistry
Xiaodong Xia, Jiao Li, Xue Liang, Shengjie Zhang, Tong Liu, Jinying Liu, Muhammad Arif, Guangping Li
Although ticagrelor has been demonstrated to possess an anti‑atherosclerosis (AS) effect, its underlying mechanism remains unclear. In the present study, it was investigated whether ticagrelor reduces oxidized low‑density lipoprotein (ox‑LDL)‑induced endothelial cell apoptosis, an initial step for the development of AS, and alleviates AS in apolipoprotein‑E‑deficient (ApoE‑/‑) mice by inhibiting the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9). The human endothelial cell line EAhy926 was treated with ox‑LDL, ox‑LDL + ticagrelor (40 µmol/l) and ox‑LDL + ticagrelor (60 µmol/l) for 24 h...
December 20, 2018: Molecular Medicine Reports
Yao Liu, Xu Wang, Juan Pang, Hanyue Zhang, Jing Luo, Xiaoyun Qian, Qian Chen, Wenhua Ling
Macrophage polarization has a vital impact on the progression of atherosclerosis (AS). Protocatechuic acid (PCA), a flavonol, displays notable atheroprotective effects, but its mechanisms have not been clearly defined. We investigated whether PCA attenuated AS by regulating macrophage polarization. PCA consumption inhibited HCD-induced plaque formation (17.84% and 8.21% in the HCD and HCD+PCA groups, respectively; p < 0.05) and inflammatory responses in apolipoprotein E-deficient (ApoE-/-) mice. Moreover, PCA suppressed the classically activated macrophage (M1) polarization, which decreased the secretion of synthesis of nitric oxide synthase (54...
December 28, 2018: Journal of Agricultural and Food Chemistry
Magalí Barchuk, Verónica Miksztowicz, Valeria Zago, Agata Cevey, Graciela López, Nora Goren, Silvia Friedman, Ricardo Jorge Gelpi, Celina Morales, María Del Carmen Fernandez Tomé, Laura Schreier, Gabriela Berg
Lipoprotein lipase (LPL) and endothelial lipase (EL) are involved in lipoprotein metabolism. In insulin-resistance, their behavior is altered. Peroxisome proliferator-activated receptors (PPAR) and apoproteins (apo)CII and CIII could be partly responsible for these alterations. To evaluate this response, we assessed Lpl and Lipg expression, protein levels, and enzyme activity in adipose tissue (AT) and heart in an obesity model. Besides, we assessed the role of PPAR and apoC. Male Wistar rats were fed with standard diet (Control, n = 14) or high-fat diet (HFD, n = 14) for 14 weeks...
October 2018: Lipids
Aleksandr E Vendrov, Arihiro Sumida, Chandrika Canugovi, Andrey Lozhkin, Takayuki Hayami, Nageswara R Madamanchi, Marschall S Runge
Increased reactive oxygen species (ROS) production and inflammation are key factors in the pathogenesis of atherosclerosis. We previously reported that NOX activator 1 (NOXA1) is the critical functional homolog of p67phox for NADPH oxidase activation in mouse vascular smooth muscle cells (VSMC). Here we investigated the effects of systemic and SMC-specific deletion of Noxa1 on VSMC phenotype during atherogenesis in mice. Neointimal hyperplasia following endovascular injury was lower in Noxa1-deficient mice versus the wild-type following endovascular injury...
November 29, 2018: Redox Biology
Tsuyoshi Goto
Obesity is one of the most important risk factors for chronic metabolic disorders. Molecular mechanisms underlying obesity-related metabolic disorders have not been completely elucidated. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and are key metabolic regulators of the whole-body energy metabolism. Certain enzymes involved in carbohydrate and lipid metabolism are directly regulated by PPARs via their interaction with specific response elements in their gene promoters...
December 20, 2018: Bioscience, Biotechnology, and Biochemistry
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