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https://www.readbyqxmd.com/read/28099257/antifibrotic-effect-of-saturated-fatty-acids-via-endoplasmic-reticulum-stress-response-in-rat-pancreatic-stellate-cells
#1
Lingaku Lee, Tetsuhide Ito, Taichi Nakamura, Robert T Jensen, Hisato Igarashi, Ryoichi Takayanagi
OBJECTIVES: We investigated the effect of saturated fatty acids on chronic pancreatitis pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis. METHODS: Wistar Bonn/Kobori rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin, an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability, and apoptosis were examined...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28068410/leukotriene-b%C3%A2-metabolism-and-p70s6-kinase-1-inhibitors-pf-4708671-but-not-ly2584702-inhibits-cyp4f3a-and-the-%C3%AF-oxidation-of-leukotriene-b%C3%A2-in-vitro-and-in-cellulo
#2
Anne-Sophie Archambault, Caroline Turcotte, Cyril Martin, Julie S Lefebvre, Véronique Provost, Michel Laviolette, Nicolas Flamand
LTB4 is an inflammatory lipid mediator mainly biosynthesized by leukocytes. Since its implication in inflammatory diseases is well recognized, many tools to regulate its biosynthesis have been developed and showed promising results in vitro and in vivo, but mixed results in clinical trials. Recently, the mTOR pathway component p70S6 kinase 1 (p70S6K1) has been linked to LTC4 synthase and the biosynthesis of cysteinyl-leukotrienes. In this respect, we investigated if p70S6K1 could also play a role in LTB4 biosynthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28065589/perk-and-xbp1-differentially-regulate-cxcl10-and-ccl2-production
#3
Shuang Zhu, Hua Liu, Haibo Sha, Ling Qi, Dian-Shuai Gao, Wenbo Zhang
Inflammation plays a key role in the pathogenesis of many retinal degenerative diseases related with photoreceptor dysfunction/degeneration. However the involvement of photoreceptor cells in inflammatory reactions is largely unknown as they are not considered as inflammatory cells. In this study, we assessed whether photoreceptor cells can produce CCL2 and CXCL10, two important players in inflammation during endoplasmic reticulum (ER) stress. After photoreceptor 661 W cells were treated with ER stress inducer thapsigargin (TG), induction of ER stress increased CXCL10 and CCL2 expression at both mRNA and protein levels, which was significantly blocked by an ER stress blocker 4-phenylbutyrate...
January 5, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28052644/effect-of-thymol-on-ca%C3%A2-%C3%A2-%C2%BA-homeostasis-and-viability-in-pc3-human-prostate-cancer-cells
#4
Jeng-Hsien Yeh, Chiang-Ting Chou, I-Shu Chen, Ti Lu, Ko-Long Lin, Chia-Cheng Yu, Wei-Zhe Liang, Hong-Tai Chang, Chun-Chi Kuo, Chin-Man Ho, Wen-Teng Chang, Pochuen Shieh, Chung-Ren Jan
Thymol is a phenolic compound that affects physiology in different cell models. However, whether thymol affects Ca²⁺ homeostasis in prostate cancer cells is unknown. The action of this compound on cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and viability in PC3 human prostate cancer cells was explored. The results show that thymol at concentrations of 100-1500 μM caused [Ca²⁺]i rises in a concentration-dependent manner. Removal of extracellular Ca²⁺ reduced thymol’s effect by approximately 80%...
28, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28038379/high-density-lipoprotein-hdl-associated-sphingosine-1-phosphate-s1p-inhibits-macrophage-apoptosis-by-stimulating-stat3-activity-and-survivin-expression
#5
Renata Feuerborn, Susen Becker, Francesco Potì, Petra Nagel, Martin Brodde, Harmut Schmidt, Christina Christoffersen, Uta Ceglarek, Ralph Burkhardt, Jerzy-Roch Nofer
BACKGROUND AND AIMS: Macrophage apoptosis is critically involved in atherosclerosis. We here examined the effect of anti-atherogenic high density lipoprotein (HDL) and its component sphingosine-1-phosphate (S1P) on apoptosis in RAW264.7 murine macrophages. METHODS: Mitochondrial or endoplasmic reticulum-dependent apoptosis was induced by exposure of macrophages to etoposide or thapsigargin/fukoidan, respectively. RESULTS: Cell death induced by these compounds was inhibited by S1P as inferred from reduced annexin V binding, TUNEL staining, and caspase 3, 9 and 12 activities...
December 9, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28025169/evaluation-of-in%C3%A2-vitro-toxicity-of-polymeric-micelles-to-human-endothelial-cells-under-different-conditions
#6
Fang Liu, Haikang Huang, Yu Gong, Juan Li, Xuefei Zhang, Yi Cao
Polymeric micelles have been extensively studied in the area of antitumor therapy, and more recently explored as nanocarriers for atherosclerosis. These applications of polymeric micelles in biomedicine will increase their contact with human blood vessels. However, few studies have considered the interactions between polymeric micelles and endothelial cells, especially in a complex system. This study used human umbilical vein endothelial cells (HUVECs) as an in vitro model for endothelial cells to investigate the toxic effects of methoxy-poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) based micelles...
December 23, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28012209/link-between-er-stress-ppar-alpha-activation-and-bet-inhibition-in-relation-to-apolipoprotein-a-i-transcription-in-hepg2-cells
#7
Sophie E van der Krieken, Herman E Popeijus, Ronald P Mensink, Jogchum Plat
Activating transcription factor peroxisome proliferator-activated receptor alpha (PPARα) may increase apoA-I transcription. Furthermore, Bromodomain and Extra-Terminal domain (BET) protein inhibitors increase, whereas Endoplasmic Reticulum (ER) stress decreases apoA-I transcription. We examined possible links between these processes as related to apoA-I transcription in HepG2 cells. JQ1(+), thapsigargin and GW7647 were used to induce respectively BET inhibition, ER-stress and PPARα activation. Expression of ER-stress markers (CHOP, XBP1s) was analyzed by western blotting...
December 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27997269/the-effects-of-endoplasmic-reticulum-stress-inducer-thapsigargin-on-the-toxicity-of-zno-or-tio2-nanoparticles-to-human-endothelial-cells
#8
Yuxiu Gu, Shanshan Cheng, Gui Chen, Yuexin Shen, Xiyue Li, Qin Jiang, Juan Li, Yi Cao
It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO2 NPs were used to compare the effects...
December 20, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27992581/gadd34-keeps-the-mtor-pathway-inactivated-in-endoplasmic-reticulum-stress-related-autophagy
#9
Marianna Holczer, Gábor Bánhegyi, Orsolya Kapuy
The balance of protein synthesis and proteolysis (i.e. proteostasis) is maintained by a complex regulatory network in which mTOR (mechanistic target of rapamycin serine/threonine kinase) pathway and unfolded protein response are prominent positive and negative actors. The interplay between the two systems has been revealed; however the mechanistic details of this crosstalk are largely unknown. The aim of the present study was to investigate the elements of crosstalk during endoplasmic reticulum stress and to verify the key role of GADD34 in the connection with the mTOR pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27986562/free-fatty-acids-or-high-concentration-glucose-enhances-hepatitis-a-virus-replication-in-association-with-a-reduction-in-glucose-regulated-protein-78-expression
#10
Nan Nwe Win, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Hiroaki Okamoto, Osamu Yokosuka, Hiroshi Shirasawa
Although the interaction between host and hepatitis A virus (HAV) factors could lead to severe hepatitis A, the exact mechanism of acute liver failure caused by HAV infection is not yet fully understood. The effects of metabolic diseases such as dyslipidemia or diabetes mellitus on HAV replication are still unknown. Here, we examined the effects of free fatty acids or high-concentration glucose on HAV replication and the effects on mitogen-activated protein kinase signaling pathway-related genes in human hepatocytes...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27982302/successful-application-of-virtual-screening-and-molecular-dynamics-simulations-against-antimalarial-molecular-targets
#11
Renata Rachide Nunes, Marina Dos Santos Costa, Bianca Dos Reis Santos, Amanda Luisa da Fonseca, Lorena Sales Ferreira, Rafael Cesar Russo Chagas, Alisson Marques da Silva, Fernando de Pilla Varotti, Alex Gutterres Taranto
The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001) against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC) were established for each molecular target...
December 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/27975992/domesticating-deadly-carrots-predicting-the-biosynthetic-pathway-of-thapsigargins-for-the-treatment-of-solid-tumors
#12
K Martinez, H T Simonsen, N Rønsted, T Bundgaard Andersen, C Barnes, B Boughton, F Cozzi
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27960157/chorein-sensitive-orai1-expression-and-store-operated-ca2-entry-in-rhabdomyosarcoma-cells
#13
Willi Yu, Sabina Honisch, Sebastian Schmidt, Jing Yan, Evi Schmid, Saad Alkahtani, Abdullah A AlKahtane, Saud Alarifi, Christos Stournaras, Florian Lang
BACKGROUND: Chorein, a protein encoded by VPS13A (vacuolar protein sorting-associated protein 13A), is defective in chorea acanthocytosis, a rare disease characterized by acanthocytosis of red blood cells and neuronal cell death with progressive hyperkinetic movement disorder, cognitive dysfunction, behavioral abnormalities and chronic hyperkalemia. Chorein is highly expressed in ZF rhabdomyosarcoma cells and counteracts apoptosis of those cells. Chorein is effective in part by interacting with and fostering stimulation of phosphoinositide-3-kinase (PI3K)-p85-subunit...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27958308/protective-effect-of-mild-endoplasmic-reticulum-stress-on-radiation-induced-bystander-effects-in-hepatocyte-cells
#14
Yuexia Xie, Shuang Ye, Jianghong Zhang, Mingyuan He, Chen Dong, Wenzhi Tu, Peifeng Liu, Chunlin Shao
Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the defense and self-protective mechanisms of bystander normal cells are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 cells under either normoxia or hypoxia, where the ratio of the yield of bystander MN induction to the yield of radiation-induced MN formation under hypoxia was much higher than that of normoxia...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27940503/inhibition-of-nonsense-mediated-rna-decay-by-er-stress
#15
Zhelin Li, John K Vuong, Min Zhang, Cheryl Stork, Sika Zheng
Nonsense-mediated RNA decay (NMD) selectively degrades mutated and aberrantly processed transcripts that contain premature termination codons (PTC). Cellular NMD activity is typically assessed using exogenous PTC-containing reporters. We overcame some inherently problematic aspects of assaying endogenous targets and developed a broadly applicable strategy to reliably and easily monitor changes in cellular NMD activity. Our new method was genetically validated for distinguishing NMD regulation from transcriptional control and alternative splicing regulation, and unexpectedly disclosed different sensitivity of NMD targets to NMD inhibition...
December 9, 2016: RNA
https://www.readbyqxmd.com/read/27939990/apomorphine-prevents-lps-induced-il-23-p19-mrna-expression-via-inhibition-of-jnk-and-atf4-in-hapi-cells
#16
Hirokazu Hara, Dai Kimoto, Miho Kajita, Chisato Takada, Tetsuro Kamiya, Tetsuo Adachi
Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal injury. Interleukin (IL)-23, which consists of p19 and IL-12 p40 subunits, has been shown to be involved in brain injury associated with neuroinflammation. Apomorphine (Apo), a nonselective dopamine receptor agonist, has been used for clinical therapy of Parkinson's disease...
December 9, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27939335/calcium-signalling-induced-by-in-vitro-exposure-to-silicium-dioxide-nanoparticles-in-rat-pulmonary-artery-smooth-muscle-cells
#17
Virginie Dubes, Thibaud Parpaite, Thomas Ducret, Jean-François Quignard, Stéphane Mornet, Nora Reinhardt, Isabelle Baudrimont, Mathilde Dubois, Véronique Freund-Michel, Roger Marthan, Bernard Muller, Jean-Pierre Savineau, Arnaud Courtois
The development and use of nanomaterials, especially engineered nanoparticles (NP), is expected to provide many benefits. But at the same time the development of such materials is also feared because of their potential human health risks. Indeed, NP display some characteristics similar to ultrafine environmental particles which are known to exert deleterious cardiovascular effects including pro-hypertensive ones. In this context, the effect of NP on calcium signalling, whose deregulation is often involved in hypertensive diseases, remain poorly described...
January 15, 2017: Toxicology
https://www.readbyqxmd.com/read/27928013/herpes-simplex-virus-1-ul41-protein-suppresses-the-ire1-xbp1-signal-pathway-of-the-unfolded-protein-response-via-its-rnase-activity
#18
Pengchao Zhang, Chenhe Su, Zhangtao Jiang, Chunfu Zheng
: During viral infection, accumulation of viral proteins can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR) to restore the ER homeostasis. Inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved one of the three UPR signal pathways. Upon activation, IRE1 splices out an intron from the unspliced inactive form X-box binding protein 1 (XBP1(u)) mRNA and produces a transcriptionally potent spliced form (XBP1(s)). Previous studies have reported that the IRE1/XBP1 pathway is inhibited upon herpes simplex virus 1 (HSV-1) infection, however, the underlying molecular mechanism is still illusive...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#19
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Sarka Lhotak, Pei Yu, Gabriel Gyulay, Guillaume Paré, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil G Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER localized transcription factor that directly upregulates sterol-regulatory genes, including PCSK9. Given that PCSK9 contributes to atherosclerosis by targeting low-density lipoprotein (LDL) receptor (LDLR) degradation, our present study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907038/equol-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice-by-inhibiting-endoplasmic-reticulum-stress-via-activation-of-nrf2-in-endothelial-cells
#20
Ting Zhang, Qin Hu, Linying Shi, Li Qin, Qianyong Zhang, Mantian Mi
The development of atherosclerosis is closely related to excessive endoplasmic reticulum stress (ERs). Equol reportedly protects against cardiovascular disease; however, the underlying mechanism for this protection remains unknown. Herein, the mechanisms contributing to the atheroprotective effect of equol were addressed using apolipoprotein E knockout (apoE-/-) mice fed a high-fat diet (HFD) with or without equol. Equol intervention reduced atherosclerotic lesions in the aorta in HFD-fed apoE-/- mice. Plasma lipid analysis showed that equol intervention reduced triglycerides, total cholesterol and LDL-cholesterol and increased HDL-cholesterol...
2016: PloS One
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