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https://www.readbyqxmd.com/read/28622297/p53-mediated-suppression-of-bip-triggers-bik-induced-apoptosis-during-prolonged-endoplasmic-reticulum-stress
#1
Ignacio López, Anne-Sophie Tournillon, Rodrigo Prado Martins, Konstantinos Karakostis, Laurence Malbert-Colas, Karin Nylander, Robin Fåhraeus
Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28616035/neuroprotective-effects-of-activin-a-on-endoplasmic-reticulum-stress-mediated-apoptotic-and-autophagic-pc12-cell-death
#2
Long-Xing Xue, Hong-Yu Liu, Yang Cui, Yue Dong, Jiao-Qi Wang, Qiu-Ye Ji, Jin-Ting He, Min Yao, Ying-Ying Wang, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A, a member of the transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases. Endoplasmic reticulum (ER) stress-mediated apoptotic and autophagic cell death is implicated in a wide range of diseases, including cerebral ischemia and neurodegenerative diseases. Thapsigargin was used to induce PC12 cell death, and Activin A was used for intervention. Our results showed that Activin A significantly inhibited morphological changes in thapsigargin-induced apoptotic cells, and the expression of apoptosis-associated proteins [cleaved-caspase-12, C/EBP homologous protein (CHOP) and cleaved-caspase-3] and biomarkers of autophagy (Beclin-1 and light chain 3), and downregulated the expression of thapsigargin-induced ER stress-associated proteins [inositol requiring enzyme-1 (IRE1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38]...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615521/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#3
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604593/melatonin-modulates-neuronal-cell-death-induced-by-endoplasmic-reticulum-stress-under-insulin-resistance-condition
#4
Juhyun Song, Oh Yoen Kim
Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells...
June 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28593135/evaluation-of-cell-death-pathways-initiated-by-antitumor-drugs-melatonin-and-valproic-acid-in-bladder-cancer-cells
#5
Siwei Liu, Bilin Liang, Huiting Jia, Yuhan Jiao, Zhongqiu Pang, Yongye Huang
Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid (VPA) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up-regulation of certain genes related to apoptosis (TNFRSF10A and TNFRSF10B), autophagy (BECN, ATG3 and ATG5) and necrosis (MLKL, PARP-1 and RIPK1)...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28591178/unfolded-protein-response-plays-a-critical-role-in-heart-damage-after-myocardial-ischemia-reperfusion-in-rats
#6
Chengcheng Zhang, Yi Tang, Yanming Li, Liang Xie, Wei Zhuang, Jing Liu, Jianbin Gong
The unfolded protein response (UPR) plays a critical role in cell death mediated by ischemia/reperfusion (I/R) injury. However, little is known about the exact mechanism of UPR signaling pathways after myocardial I/R injury in rats. An attempt was therefore made to assess whether the myocardial I/R induced UPR, and which branch of UPR (ATF6, IRE1 and PERK) signal pathway was activated. Sprague-Dawley rats were pretreated with UPR stimulator dithiothreitol (DTT) and UPR inhibitor 4-phenylbutyrate (4PBA) and then subjected to myocardial I/R surgery...
2017: PloS One
https://www.readbyqxmd.com/read/28588081/intercellular-transmission-of-the-unfolded-protein-response-promotes-survival-and-drug-resistance-in-cancer-cells
#7
Jeffrey J Rodvold, Kevin T Chiu, Nobuhiko Hiramatsu, Julia K Nussbacher, Valentina Galimberti, Navin R Mahadevan, Karl Willert, Jonathan H Lin, Maurizio Zanetti
Increased protein translation in cells and various factors in the tumor microenvironment can induce endoplasmic reticulum (ER) stress, which initiates the unfolded protein response (UPR). We have previously reported that factors released from cancer cells mounting a UPR induce a de novo UPR in bone marrow-derived myeloid cells, macrophages, and dendritic cells that facilitates protumorigenic characteristics in culture and tumor growth in vivo. We investigated whether this intercellular signaling, which we have termed transmissible ER stress (TERS), also operates between cancer cells and what its functional consequences were within the tumor...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28583762/puerarin-inhibits-amyloid-%C3%AE-induced-nlrp3-inflammasome-activation-in-retinal-pigment-epithelial-cells-via-suppressing-ros-dependent-oxidative-and-endoplasmic-reticulum-stresses
#8
Ke Wang, Xue Zhu, Kai Zhang, Yong Yao, Miao Zhuang, Chengye Tan, Fanfan Zhou, Ling Zhu
Amyloid β (Aβ) is a critical stimulator that promotes the progression of age-related macular degeneration (AMD). NLRP3 inflammasome activation induced by Aβ is estimated to be responsible for retinal pigment epithelium (RPE) dysfunction in such disease. Puerarin, one of the major active constituents of Kudzu root, has been widely used in the clinical treatment of AMD in China for decades; however, the detailed molecular mechanism remains far from clear. In this study, we investigated the protective effect and underlying mechanism of puerarin against Aβ1-40-induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells...
June 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28559891/systematic-optimization-of-protein-secretory-pathways-in-saccharomyces-cerevisiae-to-increase-expression-of-hepatitis-b-small-antigen
#9
Jiayuan Sheng, Hunter Flick, Xueyang Feng
Hepatitis B is a major disease that chronically infects millions of people in the world, especially in developing countries. Currently, one of the effective vaccines to prevent Hepatitis B is the Hepatitis B Small Antigen (HBsAg), which is mainly produced by the recombinant yeast Saccharomyces cerevisiae. In order to bring down the price, which is still too high for people in developing countries to afford, it is important to understand key cellular processes that limit protein expression. In this study, we took advantage of yeast knockout collection (YKO) and screened 194 S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28559428/bypass-of-activation-loop-phosphorylation-by-aspartate-836-in-activation-of-the-endoribonuclease-activity-of-ire1
#10
Michael C Armstrong, Sergej Šestak, Ahmed A Ali, Hanan A M Sagini, Max Brown, Karen Baty, Achim Treumann, Martin Schröder
The bifunctional protein kinase-endoribonuclease Ire1 initiates splicing of the mRNA for the transcription factor Hac1 when unfolded proteins accumulate in the endoplasmic reticulum. Activation of Saccharomyces cerevisiae Ire1 coincides with autophosphorylation of its activation loop at S840, S841, T844, and S850. Mass spectrometric analysis of Ire1 expressed in Escherichia coli identified S837 as another potential phosphorylation site in vivo Mutation of all five potential phosphorylation sites in the activation loop decreased, but did not completely abolish, splicing of HAC1 mRNA, induction of KAR2 and PDI1 mRNAs, and expression of a β-galactosidase reporter activated by Hac1(i) Phosphorylation site mutants survive low levels of ER stress better than IRE1 deletions strains...
May 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28546432/regulation-of-the-endoplasmic-reticulum-stress-response-and-neuroprotective-effects-of-acupuncture-on-brain-injury-caused-by-heroin-addiction
#11
Yong-Long Gao, Yang Zhang, Jiang-Peng Cao, Sheng-Bing Wu, Xing-Hui Cai, Yan-Chun Zhang, Rong-Jun Zhang, Xiao-Ge Song, Li-Da Zhang
OBJECTIVES: To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group...
May 25, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/28535855/japanese-encephalitis-virus-activates-autophagy-through-xbp1-and-atf6-er-stress-sensors-in-neuronal-cells
#12
Manish Sharma, Sankar Bhattacharyya, Kiran Bala Sharma, Shailendra Chauhan, Suramya Asthana, Malik Zainul Abdin, Sudhanshu Vrati, Manjula Kalia
Endoplasmic reticulum (ER) stress and autophagy are key cellular responses to RNA virus infection. Recent studies have shown that Japanese encephalitis virus (JEV)-induced autophagy negatively influences virus replication in mouse neuronal cells and embryonic fibroblasts, and delays virus-induced cell death. Here, we evaluated the role of ER stress pathways in inducing autophagy during JEV infection. We observed that JEV infection of neuronal cells led to activation of all three sensors of ER stress mediated by eIF2α/PERK, IRE1/XBP1 and ATF6...
May 23, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28488794/apoptotic-activity-of-lactobacillus-plantarum-dgk-17-fermented-soybean-seed-extract-in-human-colon-cancer-cells-via-ros-jnk-signaling-pathway
#13
Imran Khan, Sun Chul Kang
Fermented food has been always possesses upper hand compared to normal food due to its antibacterial, antioxidant, and anticancer properties. Soybeans, which have high nutritional value, are widely consumed in Korea. In this study, soybean seed powder fermented with Lactobacillus plantarum DGK-17, which was previously isolated from kimchi, showed anticancer potential. Fermented soybean extract (FSE) resulted in morphological changes, reduction of cancer cell colony formation and apoptotic cell death of HCT-116 colon cancer cells in a dose-dependent manner, and IC50 value of 111 μg...
June 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28487326/xbp1-x-box-binding-protein-1-dependent-o-glcnacylation-is-neuroprotective-in-ischemic-stroke-in-young-mice-and-its-impairment-in-aged-mice-is-rescued-by-thiamet-g
#14
Meng Jiang, Shu Yu, Zhui Yu, Huaxin Sheng, Ying Li, Shuai Liu, David S Warner, Wulf Paschen, Wei Yang
BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)...
May 9, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28485890/inhibition-of-endoplasmic-reticulum-stress-apoptosis-by-estrogen-protects-human-umbilical-vein-endothelial-cells-through-the-pi3-kinase-akt-signaling-pathway
#15
Yu Wang, Xin Yang, Xiao-Dong Li, Yong-Fen Qi, Xiao-Jing He, Yan-Jie Wang
OBJECTIVES: We aimed to investigate whether the cardioprotective effect of estrogen is mediated by inhibiting the apoptosis induced by endoplasmic reticulum stress (ERS) and to explore the underlying signaling pathway responsible for this effect. METHODS: The effect of estrogen on ERS apoptosis, the mechanism responsible for that effect, and the ERS signaling pathways were examined in human umbilical vein endothelial cells (HUVECs) and measured using western blot or Hoechst stains...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28472786/roles-of-the-exogenous-h2s-mediated-sr-a-signaling-pathway-in-renal-ischemia-reperfusion-injury-in-regulating-endoplasmic-reticulum-stress-induced-autophagy-in-a-rat-model
#16
Qing Ling, Xiao Yu, Tao Wang, Shao-Gang Wang, Zhang-Qun Ye, Ji-Hong Liu
OBJECTIVE: This study aims to explore the effects of the exogenous hydrogen sulfide (H2S)-mediated scavenger receptor A (SR-A) signaling pathway on renal ischemia/reperfusion injury (IRI) by regulating endoplasmic reticulum (ER) stress-induced autophagy in rats. METHODS: A total of 48 normal Sprague-Dawley (SD) rats and SR-A knockout rats were selected and divided into six groups (n = 8): wild-type (WT) + sham, WT + ischemia-reperfusion (I/R), WT + I/R + NaHS, SR-A-/- + sham, SR-A-/- + I/R and SR-A-/- + I/R + NaHS...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28467788/sphingosine-kinase-2-inhibition-synergises-with-bortezomib-to-target-myeloma-by-enhancing-endoplasmic-reticulum-stress
#17
Craig T Wallington-Beddoe, Melissa K Bennett, Kate Vandyke, Lorena Davies, Julia R Zebol, Paul A B Moretti, Melissa R Pitman, Duncan R Hewett, Andrew C W Zannettino, Stuart M Pitson
The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER stress and the UPR prompted us to examine potential synergy between these agents in myeloma...
April 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465244/perk-eif2%C3%AE-contributes-to-changes-of-insulin-signaling-in-hepg2-cell-induced-by-intermittent-hypoxia
#18
Huahua Yi, Chenjuan Gu, Min Li, Zhiguo Zhang, Qingyun Li, Jing Feng, Jun Zhou, Juan Du
AIMS: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with abnormal glucose metabolism. Nowadays, endoplasmic reticulum (ER) stress emerges as an important mechanism underlying the development of type 2 diabetes mellitus (T2DM). However, it remains unclear that intermittent hypoxia (IH) could induce ER stress, resulting in abnormality of glucose metabolism. Thu, in the current study we explore the changes of insulin signaling under IH and the role of ER stress underlying these changes...
April 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/28461119/taraxacum-mongolicum-extract-induced-endoplasmic-reticulum-stress-associated-apoptosis-in-triple-negative-breast-cancer-cells
#19
Xiao-Hong Li, Xi-Ran He, Yan-Yan Zhou, Hai-Yu Zhao, Wen-Xian Zheng, Shan-Tong Jiang, Qun Zhou, Ping-Ping Li, Shu-Yan Han
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. AIM OF THE STUDY: This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line...
April 28, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28459443/regulated-ire1-dependent-mrna-decay-sets-the-threshold-for-dendritic-cell-survival
#20
Simon J Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne van de Laar, Takao Iwawaki, Juan R Del Valle, Chih-Chi Andrew Hu, Bart N Lambrecht, Sophie Janssens
The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss of XBP1 impaired survival in a tissue-specific manner-while lung cDC1s die, intestinal cDC1s survive. This was not caused by differential activation of ER stress cell-death regulators CHOP or JNK...
June 2017: Nature Cell Biology
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