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https://www.readbyqxmd.com/read/28210955/the-effects-of-igf-1-on-tnf-%C3%AE-treated-drg-neurons-by-modulating-atf3-and-gap-43-expression-via-pi3k-akt-s6k-signaling-pathway
#1
Lei Zhang, Yaping Yue, Meishuo Ouyang, Huaxiang Liu, Zhenzhong Li
Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28205069/transcriptomic-analysis-of-thp-1-macrophages-exposed-to-lipoprotein-hydrolysis-products-generated-by-lipoprotein-lipase
#2
Narmadaa Thyagarajan, Jenika D Marshall, Arthur T Pickett, Clemens Schumacher, Yanbo Yang, Sherri L Christian, Robert J Brown
Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated...
February 15, 2017: Lipids
https://www.readbyqxmd.com/read/28193539/dimeric-but-not-monomeric-%C3%AE-lactalbumin-potentiates-apoptosis-by-up-regulation-of-atf3-and-reduction-of-histone-deacetylase-activity-in-primary-and-immortalised-cells
#3
Julie A Sharp, Amelia J Brennan, Galina Polekhina, David B Ascher, Christophe Lefevre, Kevin R Nicholas
α-lactalbumin is a protein of dual function found in milk of most mammals. α-lactalbumin binds β-1,4-galactosyltransferase to form the regulatory subunit for lactose synthesis and has also been shown to cause cell death. This study shows, for the first time, that α-lactalbumin isolated in a rare 28kDa dimeric form induces cell death, while 14kDa monomeric α-lactalbumin is inactive. In contrast to the casein derived and chemically induced α-lactalbumin variants, MAL and HAMLET/BAMLET, the effects of 28kDa α-lactalbumin are calcium independent and, unlike MAL and HAMLET, 28kDa α-lactalbumin dimer causes cell death of primary mammary cells and a variety of immortalised cell lines, which are committed to cell death pathways within 1-4h of exposure...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28186491/combinatorial-bzip-dimers-define-complex-dna-binding-specificity-landscapes
#4
Jose A Rodriguez-Martinez, Aaron W Reinke, Devesh Bhimsaria, Amy E Keating, Aseem Z Ansari
How transcription factor dimerization impacts DNA binding specificity is poorly understood. Guided by protein dimerization properties, we examined DNA binding specificities of 270 human bZIP pairs. DNA interactomes of 80 heterodimers and 22 homodimers revealed that 72% of heterodimer motifs correspond to conjoined half-sites preferred by partnering monomers. Remarkably, the remaining motifs are composed of variably-spaced half-sites (12%) or 'emergent' sites (16%) that cannot be readily inferred from half-site preferences of partnering monomers...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28185985/activating-transcription-factor-3-represses-cigarette-smoke-induced-il6-and-il8-expression-via-suppressing-nf-%C3%AE%C2%BAb-activation
#5
Yan-Ping Wu, Chao Cao, Yin-Fang Wu, Miao Li, Tian-Wen Lai, Chen Zhu, Yong Wang, Song-Min Ying, Zhi-Hua Chen, Hua-Hao Shen, Wen Li
Airway and lung inflammation is a fundamental hallmark of chronic obstructive pulmonary disease (COPD). Activating transcription factor 3 (ATF3) has been reported to negatively regulate many pro-inflammatory cytokines and chemokines. However, little is known about the impact of ATF3 on the inflammatory response of COPD. Since cigarette smoke (CS) is considered to be the most important risk factor in the etiology of COPD, we attempted to investigate the effects and molecular mechanisms of ATF3 in CS-induced inflammation...
February 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28177121/activating-transcription-factor-3-atf3-protects-against-lipopolysaccharide-induced-acute-lung-injury-via-inhibiting-the-expression-of-tl1a
#6
Lanlan Qian, Yunfeng Zhao, Liang Guo, Shaoying Li, Xueling Wu
Excessive inflammatory responses are critical in the pathogenesis of acute lung injury (ALI). Activating transcription factor 3 (ATF3) is a stress-induced transcriptional regulator that is a negative regulator of inflammatory responses. Therefore, we investigated the role and signaling pathways of ATF3 in lipopolysaccharide (LPS)-induced ALI in mice. The mouse macrophage RAW264.7 cells were cultured on HTS 24-Transwell filter plates in presence of ATF3 siRNA before exposure to LPS. ATF3 knock-out (KO) and wild type (WT) mice were challenged by intra-peritoneal injection of LPS (15mg/kg)...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28165887/a-small-molecule-activator-induces-ulk1-modulating-autophagy-associated-cell-death-in-triple-negative-breast-cancer
#7
Liang Ouyang, Lan Zhang, Leilei Fu, Bo Liu
ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) dataset, tissue microarray-based analyses and multiple biological evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#8
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28120235/identifying-key-genes-associated-with-hirschsprung-s-disease-based-on-bioinformatics-analysis-of-rna-sequencing-data
#9
Wei-Kang Pan, Ya-Fei Zhang, Hui Yu, Ya Gao, Bai-Jun Zheng, Peng Li, Chong Xie, Xin Ge
BACKGROUND: Hirschsprung's disease (HSCR) is a type of megacolon induced by deficiency or dysfunction of ganglion cells in the distal intestine and is associated with developmental disorders of the enteric nervous system. To explore the mechanisms of HSCR, we analyzed the RNA-sequencing data of the expansion and the narrow segments of colon tissues separated from children with HSCR. METHODS: RNA-sequencing of the expansion segments and the narrow segments of colon tissues isolated from children with HSCR was performed...
January 25, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28095324/formalin-injection-produces-long-lasting-hypersensitivity-with-characteristics-of-neuropathic-pain
#10
Ana Belen Salinas-Abarca, Sabino Hazael Avila-Rojas, Paulino Barragán-Iglesias, Jorge Baruch Pineda-Farias, Vinicio Granados-Soto
The purpose of this study was to investigate whether 1%, 2% or 5% formalin injection produce hypersensitivity with characteristics of the neuropathic pain induced by spinal nerve injury. Formalin injection (1%, 2% and 5%) produced concentration-dependent long-lasting (at least 14 days) mechanical allodynia and hyperalgesia in both paws. Likewise, L5/L6 spinal nerve ligation induced allodynia and hyperalgesia in both paws. The intensity of hypersensitivity was greater in the ipsilateral than in the contralateral paw in all models...
January 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28093456/effect-of-lipid-bound-apolipoprotein-a-i-cysteine-mutant-on-atf3-in-raw264-7-cells
#11
Yunlong Wang, Yanhui Wang, Shaoyou Jia, Qingzhe Dong, Yuanbin Chen, Shulai Lu, Lin Hou
Activating transcription factor 3 (ATF3) is a TLR-induced repressor that plays an important role in the inhibition of specific inflammatory signals. We previously constructed recombinant high density lipoproteins (rHDL) (including rHDLWT, rHDLM, rHDL228 and rHDL74) and found that rHDL74 had a strong anti-inflammatory ability. In the present study, we investigate the roles of recombinant apolipoprotein A-I (ApoA-I) (rHDLWT) and its cysteine mutant HDLs (rHDLM, rHDL228 and rHDL74) on ATF3 function in RAW264.7 cells stimulated by lipopolysaccharide...
February 28, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28082453/atf3-expression-in-cardiomyocytes-preserves-homeostasis-in-the-heart-and-controls-peripheral-glucose-tolerance
#12
Roy Kalfon, Lilach Koren, Sharon Aviram, Ortal Schwartz, Tsonwin Hai, Ami Aronheim
AIMS: Obesity and type 2 diabetes (T2D) trigger a harmful stress-induced cardiac remodeling process known as cardiomyopathy. These diseases represent a serious and widespread health problem in the Western world; however the underlying molecular basis is not clear. ATF3 is an 'immediate early' gene whose expression is highly and transiently induced in response to multiple stressors such as metabolic, oxidative, endoplasmic reticulum and inflammation, stressors that are involved in T2D cardiomyopathy...
February 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28077357/triglyceride-rich-lipoprotein-lipolysis-products-increase-blood-brain-barrier-transfer-coefficient-and-induce-astrocyte-lipid-droplets-and-cell-stress
#13
Linda L Lee, Hnin Hnin Aung, Dennis W Wilson, Steven E Anderson, John C Rutledge, Jennifer M Rutkowsky
Elevation of blood triglycerides, primarily as triglyceride-rich lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer's disease (AD). Brain microvascular endothelial cells and astrocytes, two cell components of the neurovascular unit, participate in controlling blood-brain barrier (BBB) permeability and regulating neurovascular unit homeostasis. Our studies showed that infusion of high physiological concentrations of TGRL lipolysis products (TGRL + lipoprotein lipase) activate and injure brain endothelial cells and transiently increases the BBB transfer coefficient (Ki=permeability x surface area/volume) in vivo...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28063951/transcriptomic-analysis-of-spleen-infected-with-infectious-salmon-anemia-virus-reveals-distinct-pattern-of-viral-replication-on-resistant-and-susceptible-atlantic-salmon-salmo-salar
#14
Phillip Dettleff, Thomas Moen, Nina Santi, Victor Martinez
The infectious salmon anemia virus (ISAv) produces a systemic infection in salmonids, causing large losses in salmon production. However, little is known regarding the mechanisms exerting disease resistance. In this paper, we perform an RNA-seq analysis in Atlantic salmon challenged with ISAv (using individuals coming from families that were highly susceptible or highly resistant to ISAv infection). We evaluated the differential expression of both host and ISAv genes in a target organ for the virus, i.e. the spleen...
February 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28061889/urinary-exosomal-activating-transcriptional-factor-3-as-the-early-diagnostic-biomarker-for-sepsis-induced-acute-kidney-injury
#15
Tanaporn Panich, Wiwat Chancharoenthana, Poorichaya Somparn, Jiraphorn Issara-Amphorn, Nattiya Hirankarn, Asada Leelahavanichkul
BACKGROUND: An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. METHODS: We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker...
January 7, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28059114/cigarette-smoke-extract-profoundly-suppresses-tnf%C3%AE-mediated-proinflammatory-gene-expression-through-upregulation-of-atf3-in-human-coronary-artery-endothelial-cells
#16
Jack E Teasdale, Georgina G J Hazell, Alasdair M G Peachey, Graciela B Sala-Newby, Charles C T Hindmarch, Tristan R McKay, Mark Bond, Andrew C Newby, Stephen J White
Endothelial dysfunction caused by the combined action of disturbed flow, inflammatory mediators and oxidants derived from cigarette smoke is known to promote coronary atherosclerosis and increase the likelihood of myocardial infarctions and strokes. Conversely, laminar flow protects against endothelial dysfunction, at least in the initial phases of atherogenesis. We studied the effects of TNFα and cigarette smoke extract on human coronary artery endothelial cells under oscillatory, normal laminar and elevated laminar shear stress for a period of 72 hours...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053284/microrna-494-and-atf3-the-targets-of-onconase
#17
EDITORIAL
Zbigniew Darzynkiewicz
No abstract text is available yet for this article.
December 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035074/activating-transcription-factor-3-is-crucial-for-antitumor-activity-and-to-strengthen-the-antiviral-properties-of-onconase
#18
Anna Vert, Jessica Castro, Marc Ribó, Antoni Benito, Maria Vilanova
Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8)...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28004841/the-citrus-flavonoid-naringenin-confers-protection-in-a-murine-endotoxaemia-model-through-ampk-atf3-dependent-negative-regulation-of-the-tlr4-signalling-pathway
#19
Xin Liu, Ning Wang, Shijun Fan, Xinchuan Zheng, Yongjun Yang, Yuanfeng Zhu, Yongling Lu, Qian Chen, Hong Zhou, Jiang Zheng
Excessive activation of the TLR4 signalling pathway is critical for inflammation-associated disorders, while negative regulators play key roles in restraining TLR4 from over-activation. Naringenin is a citrus flavonoid with remarkable anti-inflammatory activity, but the mechanisms underlying its inhibition of LPS/TLR4 signalling are less clear. This study investigated the molecular targets and therapeutic effects of naringenin in vitro and in vivo. In LPS-stimulated murine macrophages, naringenin suppressed the expression of TNF-α, IL-6, TLR4, inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2) and NADPH oxidase-2 (NOX2)...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27993939/glioma-derived-cancer-stem-cells-are-hypersensitive-to-proteasomal-inhibition
#20
Young Dong Yoo, Dae-Hee Lee, Hyunjoo Cha-Molstad, Hyungsin Kim, Su Ran Mun, Changhoon Ji, Seong Hye Park, Ki Sa Sung, Seung Ah Choi, Joonsung Hwang, Deric M Park, Seung-Ki Kim, Kyung-Jae Park, Shin-Hyuk Kang, Sang Cheul Oh, Aaron Ciechanover, Yong J Lee, Bo Yeon Kim, Yong Tae Kwon
Although proteasome inhibitors (PIs) are used as anticancer drugs to treat various cancers, their relative therapeutic efficacy on stem cells vs. bulk cancers remains unknown. Here, we show that stem cells derived from gliomas, GSCs, are up to 1,000-fold more sensitive to PIs (IC50, 27-70 nM) compared with their differentiated controls (IC50, 47 to »100 μM). The stemness of GSCs correlates to increased ubiquitination, whose misregulation readily triggers apoptosis. PI-induced apoptosis of GSCs is independent of NF-κB but involves the phosphorylation of c-Jun N-terminal kinase as well as the transcriptional activation of endoplasmic reticulum (ER) stress-associated proapoptotic mediators...
January 2017: EMBO Reports
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