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https://www.readbyqxmd.com/read/28808300/pterostilbene-exerts-anticancer-activity-on-non-small-cell-lung-cancer-via-activating-endoplasmic-reticulum-stress
#1
Zhiqiang Ma, Yang Yang, Shouyin Di, Xiao Feng, Dong Liu, Shuai Jiang, Wei Hu, Zhigang Qin, Yue Li, Jianjun Lv, Chongxi Fan, Xiaolong Yan, Xiaofei Li
Pterostilbene (PT), the natural dimethylated analog of resveratrol (RSV), is a potent anticarcinogen for non-small-cell lung cancer (NSCLC), but its anti-NSCLC mechanisms remain unclear. In this study, we show that PT treatment time- and dose-dependently enhanced the endoplasmic reticulum stress (ERS) signaling (i.e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines. Moreover, the decreased migratory and adhesive abilities, downregulation of intracellular glutathione (GSH) level, enhanced reactive oxygen species (ROS) generation, Caspase 3 activity and mitochondrial membrane depolarization were observed in NSCLC cells treated with PT...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28804008/perk-as-a-hub-of-multiple-pathogenic-pathways-leading-to-memory-deficits-and-neurodegeneration-in-alzheimer-s-disease
#2
REVIEW
Masuo Ohno
Cell signaling in response to an array of diverse stress stimuli converges on the phosphorylation of eukaryotic initiation factor-2α (eIF2α). In the brain, eIF2α is a hub for controlling learning and memory function and for maintaining neuronal integrity in health and disease. Among four eIF2α kinases, PERK is emerging as a key regulator for memory impairments and neurodegeneration in Alzheimer's disease (AD). Genetic and pharmacological manipulations of PERK-eIF2α signaling have revealed that the overactivation of this pathway is not a mere consequence of the neurodegenerative process but play critical roles in AD pathogenesis and the occurrence of memory deficits...
August 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28803844/the-atf6%C3%AE-arm-of-the-unfolded-protein-response-mediates-replicative-senescence-in-human-fibroblasts-through-a-cox2-prostaglandin-e2-intracrine-pathway
#3
Johanna Cormenier, Nathalie Martin, Julie Deslé, Clara Salazar-Cardozo, Albin Pourtier, Corinne Abbadie, Olivier Pluquet
Senescence is recognized as a cellular state acquired in response to various stresses. It occurs in correlation with the activation of the Unfolded Protein Response (UPR) pathway. However, the UPR targets which might relay the establishment of the senescent phenotype are not known. Herein, we investigated whether the up-regulation of the COX2 (PTGS2) limiting enzyme in the prostaglandin biosynthesis pathway, known to mediate cellular senescence in normal human fibroblasts, could be controlled by the UPR sensors ATF6α, IRE1α and PERK...
August 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28802884/astrocytes-and-endoplasmic-reticulum-stress-a-bridge-between-obesity-and-neurodegenerative-diseases
#4
REVIEW
Cynthia A Martin-Jiménez, Ángela García-Vega, Ricardo Cabezas, Gjumrakch Aliev, Valentina Echeverria, Janneth González, George E Barreto
Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis...
August 9, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28801170/pgc-1%C3%AE-in-aging-and-lifelong-exercise-training-mediated-regulation-of-upr-in-mouse-liver
#5
Caroline M Kristensen, Christina T Brandt, Stine Ringholm, Henriette Pilegaard
Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism including the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in skeletal muscle and liver. Therefore, the aim of the present study was to examine the impact of PGC-1α in aging and lifelong exercise training-induced hepatic UPR in mice...
August 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28798155/ifn-%C3%AE-aggravates-neointimal-hyperplasia-by-inducing-endoplasmic-reticulum-stress-and-apoptosis-in-macrophages-by-promoting-ubiquitin-dependent-liver-x-receptor-%C3%AE-degradation
#6
Qiang Zhao, Dong Zhou, Hongjun You, Bowen Lou, Yan Zhang, Yuling Tian, Ning Guo, Xiaoli Chen, Yan Liu, Yue Wu, Zuyi Yuan, Juan Zhou
Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN-γ and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN-γ significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-γ-treated macrophages...
August 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28796255/pdi-is-an-essential-redox-sensitive-activator-of-perk-during-the-unfolded-protein-response-upr
#7
Philip Kranz, Fabian Neumann, Alexandra Wolf, Fabian Classen, Mosche Pompsch, Tobias Ocklenburg, Jennifer Baumann, Kirsten Janke, Melanie Baumann, Kirsten Goepelt, Helena Riffkin, Eric Metzen, Ulf Brockmeier
Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#8
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28792279/resting-mapk-expression-in-chronically-trained-endurance-runners
#9
Justin X Nicoll, Andrew C Fry, Andrew J Galpin, Donald B Thomason, Christopher A Moore
PURPOSE: There is a paucity of research investigating the expression of mitogen-activated protein kinases (MAPK) in chronically trained (CT) athletes. Thus, it is unclear how MAPK may contribute to performance and muscle adaptation in CT subjects. The purpose of this study was to determine MAPK total protein, and phosphorylated expression of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38-MAPK (p38) between untrained, and chronically trained runners...
August 9, 2017: European Journal of Sport Science
https://www.readbyqxmd.com/read/28790387/gsk3%C3%AE-and-erk-regulate-the-expression-of-78%C3%A2-kda-sg2na-and-ectopic-modulation-of-its-level-affects-phases-of-cell-cycle
#10
Shweta Pandey, Indrani Talukdar, Buddhi P Jain, Shyamal K Goswami
Striatin and SG2NA are essential constituents of the multi-protein STRIPAK assembly harbouring protein phosphatase PP2A and several kinases. SG2NA has several isoforms generated by mRNA splicing and editing. While the expression of striatin is largely restricted to the striatum in brain, that of SG2NAs is ubiquitous. In NIH3T3 cells, only the 78 kDa isoform is expressed. When cells enter into the S phase, the level of SG2NA increases; reaches maximum at the G2/M phase and declines thereafter. Downregulation of SG2NA extends G1 phase and its overexpression extends G2...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790012/mdivi-1-ameliorates-early-brain-injury-after-subarachnoid-hemorrhage-via-the-suppression-of-inflammation-related-blood-brain-barrier-disruption-and-endoplasmic-reticulum-stress-based-apoptosis
#11
Lin-Feng Fan, Ping-You He, Yu-Cong Peng, Qing-Hua Du, Yi-Jun Ma, Jian-Xiang Jin, Hang-Zhe Xu, Jian-Ru Li, Zhi-Jiang Wang, Sheng-Long Cao, Tao Li, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28782832/aav-delivery-of-grp78-bip-promotes-adaptation-of-human-rpe-cell-to-er-stress
#12
Shima Ghaderi, Shahin Ahmadian, Zahra-Soheila Soheili, Hamid Ahmadieh, Shahram Samiei, Samira Kheitan, Ehsan Ranaei Pirmardan
Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration...
August 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28782427/berberine-improves-diabetic-encephalopathy-through-sirt1-er-stress-pathway-in-db-db-mice
#13
Hong-Ying Li, Xin-Chen Wang, Yu-Min Xu, Na-Chuan Luo, Si Luo, Xu-Yi Hao, Shu-Yi Cheng, Jian-Song Fang, Qi Wang, Shi-Jie Zhang, Yun-Bo Chen
The association between diabetes and dementia has been well-demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through SIRT1/endoplasmic reticulum (ER) stress pathway. The behavioral results (Morris water maze, Y-maze spontaneous alternation test and fearing condition test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability...
August 7, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28777470/crosstalk-of-er-stress-mediated-autophagy-and-er-phagy-involvement-of-upr-and-the-core-autophagy-machinery
#14
REVIEW
Shuling Song, Jin Tan, Yuyang Miao, Qiang Zhang
Endoplasmic reticulum (ER) stress, a common cellular stress response, is closely related to the activation of autophagy that is an important and evolutionarily conserved mechanism for maintaining cellular homeostasis. Autophagy induced by ER stress mainly includes the ER stress-mediated autophagy and ER-phagy. The ER stress-mediated autophagy is characterized by the generation of autophagosomes that include worn-out proteins, protein aggregates, and damaged organelles. While the autophagosomes of ER-phagy selectively include ER membranes, and the double membranes also derive, at least in part, from the ER...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28776567/-retinoic-acid-and-arsenic-trioxide-sensitize-acute-promyelocytic-leukemia-cells-to-er-stress
#15
S Masciarelli, E Capuano, T Ottone, M Divona, S De Panfilis, C Banella, N I Noguera, A Picardi, G Fontemaggi, G Blandino, F Lo-Coco, F Fazi
Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to ER stress- inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, plays a major protective role. Moreover, low amounts of pharmacologically induced ER stress, are sufficient to strongly increase ATO toxicity...
August 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28763878/-glabridin-attenuates-mptp-induced-parkinson-disease-by-inhibiting-extracellular-regulated-protein-kinases-signaling-pathway
#16
Y Zhao, Z N Lu
Objective: To investigate whether Glabridin had a beneficial effect on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) induced parkinson disease (PD) in mice, and explore the possible underlying mechanisms. Methods: Forty C57BL/6N mice were randomly assigned into control group, MPTP group, Glabridin therapy(MPTP+ GLA)group, Levodopa therapy(MPTP+ LD)group, with 10 in each group. PD model was induced by intraperitoneal administration of MPTP(20 mg/kg). The mice in MPTP+ GLA group, MPTP+ LD group and control group were gavaged by glabridin (50 mg/kg), levodopa (40 mg/kg), and equal volume of normal saline, respectively...
July 11, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28763567/low-intensity-extracorporeal-shock-wave-therapy-promotes-myogenesis-through-perk-atf4-pathway
#17
Bohan Wang, Jun Zhou, Lia Banie, Amanda B Reed-Maldonado, Hongxiu Ning, Zhihua Lu, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Guifang Wang, Stanley Lei Qi, Guiting Lin, Tom F Lue
AIM: Stress urinary incontinence (SUI) is a significant health problem for women. Treatments employing muscle derived stem cells (MDSCs) may be a promising approach to this prevalent, bothersome condition, but these treatments are invasive and require collection of cells from one site for injection into another. It is also unknown whether or not these cells establish themselves and function as muscle cells in the target tissues. Alternatively, low-intensity extracorporeal shock wave therapy (Li-ESWT) is non-invasive and has shown positive outcomes in the treatment of multiple musculoskeletal disorders, but the biological effects responsible for clinical success are not yet well understood...
August 1, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28760844/inhibitory-effect-ofquercetinon-titaniumparticle-inducedendoplasmic-reticulum-stress-ers-related-apoptosisandin-vivoosteolysis
#18
Laibo Zhang, Zhoubin Tian, Wei Li, Xianquan Wang, Zhentao Man, Shui Sun
Wear particle-induced periprosthetic osteolysis is the main cause of aseptic loosening of orthopaedic implants. The aim of this study is to determine the protective effect of quercetin (QUE) against titanium (Ti) particle-induced ERS-related apoptosis and osteolysis. In this study, RAW264.7 cells were pretreated with different concentrations (40, 80, and 160 μmol/l) of QUE for 30 min and then treated with Ti particle (5 mg/ml) for 24 h. Cell viability and apoptosis were determined using MTT assay and Annexin V-FITC apoptosis detection kit, respectively...
July 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28759991/in-silico-prediction-of-ligand-binding-energies-in-multiple-therapeutic-targets-and-diverse-ligand-sets-a-case-study-on-bace1-tyk2-hsp90-and-perk-proteins
#19
Elizabeth Hatcher Frush, Sivakumar Sekharan, Shahar Keinan
We present here the use of QM/MM LIE (Linear interaction energy) based binding free energy calculations that greatly improve the precision and accuracy of predicting experimental binding affinities, in comparison to most current binding free energy methodologies, while maintaining reasonable computational times. Calculations are done for four sets of ligand-protein complexes, chosen based on diversity of protein types and availability of experimental data, totaling 140 ligands binding to therapeutic protein targets BACE1, TYK2, HSP90 and PERK...
July 31, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28752363/inhibition-of-endoplasmic-reticulum-stress-alleviates-lung-injury-induced-by-brain-death
#20
Hongwei Tang, Jiakai Zhang, Shengli Cao, Bing Yan, Hongbo Fang, Huapeng Zhang, Wenzhi Guo, Shuijun Zhang
Brain death (BD) can induce inflammation and injury of organs. Endoplasmic reticulum (ER) stress is associated with a variety of diseases. However, little is known about how ER stress is implicated in brain death (BD)-induced lung injury. In this study, a stable BD rat model was constructed to investigate the role of ER stress on BD-induced lung injury. H&E staining demonstrated that BD can induce lung injury in rats. The results of Western blot and immunohistochemistry showed that apoptosis was observed in the lung tissues of BD rats...
July 27, 2017: Inflammation
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