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https://www.readbyqxmd.com/read/27913816/genetic-ablation-or-pharmacologic-inhibition-of-autophagy-mitigated-nsaid-associated-gastric-damages
#1
Chan Young Ock, Jong-Min Park, Young-Min Han, Migyeong Jeong, Mi-Young Kim, Ho Jae Lee, Ki Baik Hahm
: Non-steroidal anti-inflammatory drug (NSAID)-associated endoplasmic reticulum (ER) stress (a cyclooxygenase-2-independent mechanism) and consequent autophagic cell death are responsible for NSAID-associated gastric damage. Therefore, alleviating cytotoxicity executed via ER stress and autophagy can be a strategy to prevent NSAID-associated gastric damage. Here, we explored whether genetic or pharmacologic inhibition of autophagy can mitigate NSAID-associated gastric damage in in vitro and in vivo models...
December 2, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27913213/enhanced-efficacy-of-combination-heat-shock-targeted-polymer-therapeutics-with-high-intensity-focused-ultrasound
#2
Nick Frazier, Allison Payne, Christopher Dillon, Nithya Subrahmanyam, Hamidreza Ghandehari
Combination of polymer therapeutics and hyperthermia has been shown to enhance accumulation in selectively heated tumor tissue. The additional use of heat shock (HS)-targeting towards tumor tissues can further enhance accumulation and retention, and improve therapeutic outcomes. In this work, high intensity focused ultrasound (HIFU) was used to generate hyperthermia in prostate tumor tissue. Upregulation of the cell surface HS receptor glucose regulated protein 78kDa (GRP78) was observed after treatment with HIFU hyperthermia which was then targeted by specific HS-targeting peptides...
November 29, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
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
#3
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
https://www.readbyqxmd.com/read/27904664/tauroursodeoxycholic-acid-inhibits-endoplasmic-reticulum-stress-blocks-mitochondrial-permeability-transition-pore-opening-and-suppresses-reperfusion-injury-through-gsk-3%C3%A3-in-cardiac-h9c2-cells
#4
Yuxi Xie, Yonggui He, Zhiliang Cai, Jianhang Cai, Mengyao Xi, Yidong Zhang, Jinkun Xi
This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H2O2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations...
2016: American Journal of Translational Research
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
#5
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/27899042/hepatic-rhythmicity-of-endoplasmic-reticulum-stress-is-disrupted-in-perinatal-and-adult-mice-models-of-high-fat-diet-induced-obesity
#6
Junpei Soeda, Paul Cordero, Jiawei Li, Angelina Mouralidarane, Esra Asilmaz, Shuvra Ray, Vi Nguyen, Rebeca Carter, Marco Novelli, Manlio Vinciguerra, Lucilla Poston, Paul D Taylor, Jude A Oben
We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype...
November 29, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27895723/cisplatin-induced-regulation-of-signal-transduction-pathways-and-transcription-factors-in-p53-mutated-subclone-variants-of-hepatoma-cells-potential-application-for-therapeutic-targeting
#7
Jinn-Rung Kuo, Hung-Sheng Shang, Chun-Te Ho, Kun-Goung Lai, Tsan-Zon Liu, Yin-Ju Chen, Jeng-Fong Chiou
Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile antitumor effects have been demonstrated to extend beyond this narrow functional attribute. The present study determined how cisplatin regulates alternative pathways and transcription factors to exert its additional antitumor actions. Cisplatin was observed to be able to trigger an endoplasmic reticulum stress response through aggravated nitrosative stress coupled to perturbed mitochondrial calcium (Ca(2+)) homeostasis, which substantially downregulated glucose-regulated protein (GRP) 78 expression by suppressing the cleavage of activating transcription factor (ATF) 6α (90 kDa) to its active 50 kDa subunit...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894854/decreased-level-of-endogenous-ghrelin-is-involved-in-the-progression-of-lung-injury-induced-by-oleic-acid
#8
Zhijun Liu, Ting Yu, Haitao Yang, Xiuli Tian, Linlin Feng
AIMS: Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate the role of endogenous ghrelin in the pathogenesis of ALI. MAIN METHODS: We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression of ghrelin was measured by quantitative real-time PCR...
November 25, 2016: Life Sciences
https://www.readbyqxmd.com/read/27888630/the-association-of-variants-in-pnpla3-and-grp78-and-the-risk-of-developing-hepatocellular-carcinoma-in-an-italian-population
#9
Daniele Balasus, Michael Way, Caterina Fusilli, Tommaso Mazza, Marsha Y Morgan, Melchiorre Cervello, Lydia Giannitrapani, Maurizio Soresi, Rosalia Agliastro, Manlio Vinciguerra, Giuseppe Montalto
Hepatocellular carcinoma (HCC) has one of the worst prognoses amongst all malignancies. It commonly arises in patients with established liver disease and the diagnosis often occurs at an advanced stage. Genetic variations, such as single nucleotide polymorphisms (SNPs), may alter disease risk and thus may have use as predictive markers of disease outcome. The aims of this study were (i) to assess the association of two SNPs, rs430397 in GRP78 and rs738409 in PNPLA3 with the risk of developing HCC in a Sicilian association cohort and, (ii) to use a machine learning technique to establish a predictive combinatorial phenotypic model for HCC including rs430397 and rs738409 genotypes and clinical and laboratory attributes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888615/unconjugated-secondary-bile-acids-activate-the-unfolded-protein-response-and-induce-golgi-fragmentation-via-a-src-kinase-dependant-mechanism
#10
Ruchika Sharma, Francis Quilty, John F Gilmer, Aideen Long, Anne-Marie Byrne
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885588/a-mouse-model-reveals-that-mfsd2a-is-critical-for-unfolded-protein-response-upon-exposure-to-tunicamycin
#11
Hiroshi Moritake, Megumi Obara, Yusuke Saito, Ayako Kashimada, Masatoshi Takagi, Megumi Funakoshi-Tago, Tomofusa Fukuyama, Mikio Yoshioka, Akira Inoue, Hiroyuki Komatsu, Hideki Nishitoh, Hiroaki Kataoka, Hiroyuki Nunoi
Major facilitator superfamily domain containing 2a (Mfsd2a) is a member of the major facilitator superfamily. Mfsd2a functions as a transporter for docosahexaenoic acid and also plays a role in the unfolded protein response (UPR) upon tunicamycin (TM) exposure. UPR is involved in the pathogenesis of various human diseases. TM and thapsigargin are representative experimental reagents that induce UPR. To elucidate the detailed function of Mfsd2a in UPR in vivo, we generated Mfsd2a-deficient mice and investigated the role of Mfsd2a during UPR induced by TM or thapsigargin...
November 24, 2016: Human Cell
https://www.readbyqxmd.com/read/27882945/adiponectin-reduces-er-stress-induced-apoptosis-through-ppar%C3%AE-transcriptional-regulation-of-atf2-in-mouse-adipose
#12
Zhenjiang Liu, Lu Gan, Tianjiao Wu, Fei Feng, Dan Luo, Huihui Gu, Shimin Liu, Chao Sun
Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca(2+) level...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27877136/novel-role-of-er-stress-and-autophagy-in-microcystin-lr-induced-apoptosis-in-chinese-hamster-ovary-cells
#13
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/27871808/new-mechanism-of-lipotoxicity-in-diabetic-cardiomyopathy-deficiency-of-endogenous-h2s-production-and-er-stress
#14
Runmin Guo, Zijun Wu, Jiamei Jiang, Chang Liu, Bin Wu, Xingyue Li, Teng Li, Hailiang Mo, Songjian He, Shanghai Li, Hai Yan, Ruina Huang, Qiong You, Keng Wu
OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay...
November 18, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27862401/identification-and-changes-in-the-seasonal-concentrations-of-heat-shock-proteins-in-roe-deer-capreolus-capreolus-epididymides
#15
A M Majewska, W Kordan, M Koziorowska-Gilun, P Wysocki
Heat shock proteins (HSPs) act as molecular chaperones with important regulatory functions. HSPs are considered to be essential factors in animal reproduction. In view of seasonal variations in the secretory activity of the reproductive tract of mature roe deer (Capreolus capreolus), the aims of this study were to identify HSPs in the epididymides and compare the expression of the identified proteins in three periods of the reproductive season. Two-dimensional polyacrylamide gel electrophoresis revealed the highest number of polypeptides in homogenates of epididymal tissues and in caput, corpus and cauda epididymal fluids throughout the reproductive season...
November 13, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27856749/in-vivo-amelioration-of-endogenous-antitumor-autoantibodies-via-low-dose-p4n-through-the-lta4h-activin-a-baff-pathway
#16
Yu-Ling Lin, Nu-Man Tsai, Cheng-Hao Hsieh, Shu-Yi Ho, Jung Chang, Hsin-Yi Wu, Ming-Hua Hsu, Chia-Ching Chang, Kuang-Wen Liao, Tiffany L B Jackson, David E Mold, Ru Chih C Huang
Cancer progression is associated with the development of antitumor autoantibodies in patients' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27852055/isochaihulactone-induced-ddit3-causes-er-stress-perk-independent-apoptosis-in-glioblastoma-multiforme-cells
#17
Sheng-Feng Tsai, Michael Tao, Li-Ing Ho, Tzyy-Wen Chiou, Shinn-Zong Lin, Hong-Lin Su, Horng-Jyh Harn
The endoplasmic reticulum (ER) is a major site of cellular homeostasis regulation. Under the ER stress condition, Glioblastoma multiform (GBM) cells activate the unfolded protein response. In this study, we discovered isochaihulactone, a natural compound extracted from the Chinese traditional herb Nan-Chai-Hu, which can disrupt ER homeostasis in GBM cell lines. It can induce DNA damage inducible transcript 3 (DDIT3) expression which is independent of 78 kDa glucose-regulated protein (GRP78) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846717/-endoplasmic-reticulum-chaperones-at-the-tumor-cell-surface-and-in-the-extracellular-space
#18
V Brychtová, B Vojtěšek
BACKGROUND: Endoplasmic reticulum chaperones are stress induced proteins capable of translocation into cytosol, cell membrane or extracellular space. The chaperones are transported from the endoplasmic reticulum particularly under endoplasmic reticulum stress conditions, while their constitutive extracellular expression was found in many cancers. Cell surface or extracellular endoplasmic reticulum chaperones take up distinct functions compared to their endoplasmic reticulum resident variants because they act like multifunctional receptors and thus affect cell signaling and proliferation...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27845899/bisdemethoxycurcumin-exerts-pro-apoptotic-effects-in-human-pancreatic-adenocarcinoma-cells-through-mitochondrial-dysfunction-and-a-grp78-dependent-pathway
#19
Haopeng Yang, Shengjun Fan, Yu An, Xin Wang, Yan Pan, Yilixiati Xiaokaiti, Jianhui Duan, Xin Li, Lu Tie, Min Ye, Xuejun Li
Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC...
November 10, 2016: Oncotarget
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
#20
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
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