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https://www.readbyqxmd.com/read/27911441/sirt1-protects-the-heart-from-er-stress-induced-cell-death-through-eif2%C3%AE-deacetylation
#1
Alexandre Prola, Julie Pires Da Silva, Arnaud Guilbert, Lola Lecru, Jérôme Piquereau, Maxance Ribeiro, Philippe Mateo, Mélanie Gressette, Dominique Fortin, Céline Boursier, Cindy Gallerne, Anaïs Caillard, Jane-Lise Samuel, Hélène François, David A Sinclair, Pierre Eid, Renée Ventura-Clapier, Anne Garnier, Christophe Lemaire
Over the past decade, endoplasmic reticulum (ER) stress has emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases including heart failure. Cardiac therapy based on ER stress modulation is viewed as a promising avenue toward effective therapies for the diseased heart. Here, we tested whether sirtuin-1 (SIRT1), a NAD(+)-dependent deacetylase, participates in modulating ER stress response in the heart. Using cardiomyocytes and adult-inducible SIRT1 knockout mice, we demonstrate that SIRT1 inhibition or deficiency increases ER stress-induced cardiac injury, whereas activation of SIRT1 by the SIRT1-activating compound STAC-3 is protective...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894091/preclinical-study-of-cinobufagin-as-a-promising-anti-colorectal-cancer-agent
#3
Xing-Sheng Lu, Yin-Biao Qiao, Ya Li, Bo Yang, Min-Bin Chen, Chun-Gen Xing
Here, we assessed the anti-colorectal cancer (CRC) cell activity of cinobufagin (CBG). We found that CBG exerted potent cytotoxic and anti-proliferative activity against CRC lines (HCT-116 and HT-29) and primary human CRC cells. Meanwhile, it activated apoptosis, and disrupted cell-cycle progression in the cells. At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27881664/lipid-disequilibrium-disrupts-er-proteostasis-by-impairing-erad-substrate-glycan-trimming-and-dislocation
#4
Milton To, Clark W H Peterson, Melissa A Roberts, Jessica L Counihan, Tiffany T Wu, Mercedes S Forster, Daniel K Nomura, James A Olzmann
The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analog, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27877136/novel-role-of-er-stress-and-autophagy-in-microcystin-lr-induced-apoptosis-in-chinese-hamster-ovary-cells
#5
Shenshen Zhang, Chuanrui Liu, Yang Li, Mustapha U Imam, Hui Huang, Haohao Liu, Yongjuan Xin, Huizhen Zhang
Microcystin-LR (MC-LR) is a ubiquitous peptide that exhibits strong reproductive toxicity, although the mechanistic basis for such toxicity remains largely unknown. The present study was conducted to investigate the mechanisms underlying the adverse effects of exposure to MC-LR in Chinese hamster ovary (CHO) cells. The results showed that MC-LR inhibited the in vitro proliferation of CHO cells significantly, with an IC50 of 10 μM. Moreover, MC-LR-treated CHO cells revealed strong induction of cell cycle arrest and apoptosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27856431/endoplasmic-reticulum-proteostasis-a-key-checkpoint-in-cancer
#6
Scott A Oakes
The unfolded protein response (UPR) is an intracellular signaling network largely controlled by three endoplasmic reticulum (ER) transmembrane proteins-IRE1, PERK, and ATF6-that monitors the protein folding status of the ER and initiates corrective measures to maintain ER homeostasis. Hypoxia, nutrient deprivation, proteasome dysfunction, sustained demands on the secretory pathway or somatic mutations in its client proteins--conditions often encountered by cancer cells-can lead to the accumulation of misfolded proteins in the ER and cause "ER stress...
November 16, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27847321/aicar-activates-er-stress-dependent-apoptosis-in-gallbladder-cancer-cells
#7
Jifeng Nie, Aidong Liu, Qunya Tan, Kai Zhao, Kui Hu, Yong Li, Bin Yan, Lin Zhou
AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, its activity in human gallbladder cancer cells was evaluated here. We show that AICAR provoked significant apoptosis in human gallbladder cancer cell lines (Mz-ChA-1, QBC939 and GBC-SD) and primary gallbladder cancer cells. AICAR-induced cytotoxicity in gallbladder cancer cells appears independent of AMPK activation. Inhibition of AMPK, via AMPKα shRNA knockdown or dominant negative mutation (T172A), failed to rescue GBC-SD cells from AICAR...
November 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27844183/evaluation-and-treatment-of-endoplasmic-reticulum-er-stress-in-right-ventricular-dysfunction-during-monocrotaline-induced-rat-pulmonary-arterial-hypertension
#8
Jing-Jing Wang, Xiang-Rong Zuo, Jian Xu, Jin-Yong Zhou, Hui Kong, Xiao-Ning Zeng, Wei-Ping Xie, Quan Cao
PURPOSE: Endoplasmic reticulum (ER) stress contributes to pulmonary artery hypertension (PAH). However, the exact roles of ER stress in right ventricular (RV) dysfunction, which is strongly associated with PAH, are largely unknown. Here, we aimed to explore how ER stress affects RV function in a rat PAH model and evaluated the effects of an ER stress inhibitor on RV dysfunction. METHODS: We examined expression changes of an ER marker: chaperone glucose-regulated protein 78 (GRP78), three ER stress sensor proteins: activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and protein kinase RNA-like endoplasmic reticulum kinase (PERK), and a key ER stress-induced apoptosis indicator: CCAAT/enhancer-binding protein homologous protein (CHOP), with inflammation indicators: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs) in RV at 3, 7, 14 and 28 days following a single dose of monocrotaline (MCT) injection, with or without a preventive treatment [4-phenylbutyric acid (PBA)]...
November 14, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27833850/baicalin-promoted-site-2-protease-and-not-site-1-protease-in-endoplasmic-reticulum-stress-induced-apoptosis-of-human-hepatocellular-carcinoma-cells
#9
Zhe Yu, Xin Luo, Chen Wang, Jianhong Ye, Shourong Liu, Lei Xie, Fei Wang, Jianfeng Bao
Baicalin (5,6-dihydroxy-7-o-glucuronide flavone) is an extract from the roots of Chinese herb Huang Qin (Scutellaria baicalensis Georgi) and is reported to have antioxidative, antiproliferative, anti-inflammatory, and anticancer activities. This study aimed to investigate the inhibitory effect of baicalin on human hepatocellular carcinoma (HCC) cells and the involvement of endoplasmic reticulum stress-induced cell apoptosis. Two human HCC cell lines, HepG2 and SMMC7221, were used in this study. The cells were incubated with baicalin solutions at various concentrations...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27824316/nickel-chloride-nicl2-in-hepatic-toxicity-apoptosis-g2-m-cell-cycle-arrest-and-inflammatory-response
#10
Hongrui Guo, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Xun Wang, Ling Zhao, Kejie Chen, Jie Deng
Up to now, the precise mechanism of Ni toxicology is still indistinct. Our aim was to test the apoptosis, cell cycle arrest and inflammatory response mechanism induced by NiCl2 in the liver of broiler chickens. NiCl2 significantly increased hepatic apoptosis. NiCl2 activated mitochondria-mediated apoptotic pathway by decreasing Bcl-2, Bcl-xL, Mcl-1, and increasing Bax, Bak, caspase-3, caspase-9 and PARP mRNA expression. In the Fas-mediated apoptotic pathway, mRNA expression levels of Fas, FasL, caspase-8 were increased...
November 5, 2016: Aging
https://www.readbyqxmd.com/read/27783936/intestinal-ire1-is-required-for-increased-triglyceride-metabolism-and-longer-lifespan-under-dietary-restriction
#11
Nuno Miguel Luis, Lifen Wang, Mauricio Ortega, Hansong Deng, Subhash D Katewa, Patrick Wai-Lun Li, Jason Karpac, Heinrich Jasper, Pankaj Kapahi
Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27774654/er-stress-in-the-regulation-of-liver-diseases-involvement-of-ridd-and-mirna
#12
Harun-Or Rashid, Hyun-Kyoung Kim, Raghupatil Junjappa, Hyung-Ryong Kim, Han-Jung Chae
Compromised protein folding capacity in the endoplasmic reticulum (ER) leads to a protein traffic jam that produces a toxic environment called ER stress. However, the ER smartly handles such a critical situation by activating a cascade of proteins responsible for sensing and responding to the noxious stimuli of accumulated proteins. The ER protein load is higher in secretory cells, such as liver hepatocytes, which are thus prone to stress-mediated toxicity and various diseases, including alcohol-induced liver injury, fatty liver disease, and viral hepatitis...
October 23, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27761878/moderate-endoplasmic-reticulum-stress-activates-a-perk-and-p38-dependent-apoptosis
#13
Emily C Lumley, Acadia R Osborn, Jessica E Scott, Amanda G Scholl, Vicki Mercado, Young T McMahan, Zachary G Coffman, Jay L Brewster
The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR). In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress. Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm). Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM)...
October 20, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27758098/gold-nanoparticle-reprograms-pancreatic-tumor-microenvironment-and-inhibits-tumor-growth
#14
Sounik Saha, Xunhao Xiong, Prabir K Chakraborty, Khader Shameer, Rochelle R Arvizo, Rachel A Kudgus, Shailendra Kumar Dhar Dwivedi, Md Nazir Hossen, Elizabeth M Gillies, J David Robertson, Joel T Dudley, Raul A Urrutia, Russell G Postier, Resham Bhattacharya, Priyabrata Mukherjee
Altered tumor microenvironment (TME) arising from a bidirectional crosstalk between the pancreatic cancer cells (PCCs) and the pancreatic stellate cells (PSCs) is implicated in the dismal prognosis in pancreatic ductal adenocarcinoma (PDAC), yet effective strategies to disrupt the crosstalk is lacking. Here, we demonstrate that gold nanoparticles (AuNPs) inhibit proliferation and migration of both PCCs and PSCs by disrupting the bidirectional communication via alteration of the cell secretome. Analyzing the key proteins identified from a functional network of AuNP-altered secretome in PCCs and PSCs, we demonstrate that AuNPs impair secretions of major hub node proteins in both cell types and transform activated PSCs toward a lipid-rich quiescent phenotype...
October 19, 2016: ACS Nano
https://www.readbyqxmd.com/read/27747970/cpr5-modulates-salicylic-acid-and-unfolded-protein-response-to-manage-tradeoffs-between-plant-growth-and-stress-responses
#15
Zhe Meng, Cristina Ruberti, Zhizhong Gong, Federica Brandizzi
Completion of a plant's life cycle depends on successful prioritization of signaling favoring either growth or defense. Although hormones are pivotal regulators of growth-defense tradeoffs, the underlying signaling mechanisms remain obscure. The unfolded protein response (UPR) is essential for physiological growth as well as endoplasmic reticulum (ER)-stress management in unfavorable growth conditions. The plant UPR transducers are the kinase and ribonuclease IRE1 and the transcription factors bZIP28 and bZIP60...
October 16, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27725157/multivesicular-body-formation-enhancement-and-exosome-release-during-endoplasmic-reticulum-stress
#16
Soshi Kanemoto, Ryota Nitani, Tatsuhiko Murakami, Masayuki Kaneko, Rie Asada, Koji Matsuhisa, Atsushi Saito, Kazunori Imaizumi
The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK)...
October 7, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27721177/novel-quercetin-derivative-tef-induces-er-stress-and-mitochondria-mediated-apoptosis-in-human-colon-cancer-hct-116-cells
#17
Imran Khan, Souren Paul, Rekha Jakhar, Monika Bhardwaj, Jaehong Han, Sun Chul Kang
Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels...
October 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27718273/activation-of-upr-signaling-pathway-is-associated-with-the-malignant-progression-and-poor-prognosis-in-prostate-cancer
#18
Junnan Liu, Maolin Xiao, Jianjun Li, Delin Wang, Yunfeng He, Jiang He, Fei Gao, Li Mai, Ying Li, Yong Liang, Yuejiang Liu, Xiaoni Zhong
BACKGROUND: Currently, the role of UPR signaling in prostate cancer (PCa) is unclear. To evaluate the relationship between UPR signaling pathway and the prognosis of PCa, we explored the expression of IRE1, PERK, and ATF6 in tissues. METHODS: A total of 160 PCa and 30 benign prostate hyperplasia (BPH) tissues were collected. The expression of UPR signaling factors was assessed by immunohistochemistry. The staining characteristics were identified and evaluated for associations with clinicopathologic parameters, PSA recurrence survival, and prostate cancer-specific morality...
October 8, 2016: Prostate
https://www.readbyqxmd.com/read/27697517/neuroprotective-effects-of-cyanidin-against-a%C3%AE-induced-oxidative-and-er-stress-in-sk-n-sh-cells
#19
Sarinthorn Thummayot, Chainarong Tocharus, Apichart Suksamrarn, Jiraporn Tocharus
This study evaluated the mechanisms underlying the protective effect of cyanidin against Aβ25-35-induced neuronal cell death in SK-N-SH cells. Aβ25-35-induced neurotoxicity is characterized by a decrease in cell viability, inducing the expression of endoplasmic reticulum (ER) stress proteins; an increase in intracellular reactive oxygen species (ROS) production; and an increase in intracellular calcium release. Aβ25-35 also induces neuronal toxicity through the disturbance of ER calcium levels. Pretreatment with cyanidin significantly attenuated the Aβ25-35-induced loss of cell viability, reducing the expression of endoplasmic reticulum (ER) stress response proteins with regard to the down-regulation of the expression levels of 78 kDa glucose regulated protein (Grp78), phosphorylated forms of pancreatic ER elF2α kinase (PERK), eukaryotic initiation factor 2 α (eIF2α), and inositol-requiring enzyme 1 (IRE1), and the expression levels of X-box binding protein 1 (XBP-1), activating transcription factor 6 (ATF6), and CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP); decreased intracellular ROS production; decreased intracellular calcium release; and reduced down-regulation of the protein expression levels of calpain and cleaved caspase-12...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27686654/structural-insights-into-ire1-functions-in-the-unfolded-protein-response
#20
Jianqiong Yang, Haiqing Liu, Linfu Li, Hai Liu, Weimei Shi, Xiaoliang Yuan, Longhuo Wu
IRE1 signaling is the most evolutionarily conserved branch in the UPR. IRE1 is an ER stress sensor and provides a structure-based platform for the unfolded proteins docking, which causes the luminal domain conformational change and oligomerization. This self-association of IRE1 facilitates the phosphorylation of activation loop, which unlocks the auto-inhibition in the kinase domain. The activating mechanistic cascade is thus initiated to induce DFG-in conformational change and movement of αC-helix to the active site...
September 27, 2016: Current Medicinal Chemistry
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