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https://www.readbyqxmd.com/read/29124827/recovery-from-temporary-er-stress-in-plants-relies-on-tissue-specific-and-largely-independent-roles-of-bzip28-and-bzip60-as-well-as-an-antagonizing-function-of-bax-inhibitor1-onto-the-pro-adaptive-signaling-mediated-by-bzip28
#1
Cristina Ruberti, YaShiuan Lai, Federica Brandizzi
The unfolded protein response (UPR) is an ancient signaling pathway that commits to life-or-death outcomes in response to proteotoxic stress in the endoplasmic reticulum (ER). In plants, the membrane-tethered transcription factor bZIP28 and the ribonuclease-kinase IRE1 along with its splicing target, bZIP60, govern the two cytoprotective UPR signaling pathways known to date. The conserved ER membrane-associated BAX inhibitor1 (BI1) modulates ER stress-induced programmed cell death through yet-unknown mechanisms...
November 10, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29113324/unfolded-protein-response-signaling-impacts-macrophage-polarity-to-modulate-breast-cancer-cell-clearance-and-melanoma-immune-checkpoint-therapy-responsiveness
#2
David R Soto-Pantoja, Adam S Wilson, Kenysha Yj Clear, Brian Westwood, Pierre L Triozzi, Katherine L Cook
The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization. Specifically, PERK targeting enhanced macrophage proliferation and macrophage-mediated killing but not GRP78 or IRE1. Targeting UPR in cancer cells also differentially affected macrophage cytolytic capacity. Tumoral IRE1 or GRP78 inhibition enhanced macrophage-mediated cancer cell clearance. Conditioned media from GRP78-silenced cancer cells caused reciprocal regulation of CD80 and CD206, suggesting control of plasticity by secreted factors...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107182/identification-of-the-internal-ribosome-entry-sites-ires-of-prion-protein-gene
#3
Xiao-Nuan Luo, Qin-Qin Song, Jie Yu, Juan Song, Xin-Ling Wang, Dong Xia, Peng Sun, Jun Han
Many studies demonstrated that there are several type bands of prion protein in cells. However, the formation of different prion protein bands is elusive. After several low molecular weight bands of prion protein appeared in SMB-S15 cells infected with scrapie agent Chandler, we think that IRES-dependent translation mechanism induced by prion is involved in the formation of prion protein bands. Then we designed a series of pPrP-GFP fusing plasmids and bicistronic plasmids to identify the IRES sites of prion protein gene and found 3 IRES sites inside of PrP mRNA...
October 26, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29107025/association-of-changes-in-er-stress-mediated-signaling-pathway-with-lead-induced-insulin-resistance-and-apoptosis-in-rats-and-their-prevention-by-a-type-dimeric-epigallocatechin-3-gallate
#4
Chan-Min Liu, Jie-Qiong Ma, Jian-Mei Sun, Zhao-Jun Feng, Chao Cheng, Wei Yang, Hong Jiang
A-type dimeric epigallocatechin-3-gallate (A-type-EGCG-dimer, AEd), a new proanthocyanidins dimer from persimmon fruits, has been shown to have health benefit effects. However, A-type-EGCG-dimer affects gluose metabolism in the liver and the underlying mechanism is not clarified. The present study aims to examine the protective effects of A-type-EGCG-dimer on Pb-induced hepatic insulin resistance, endoplasmic reticulum (ER) stress and apoptosis in rats. Male wistar rats exposed to 0.05% w/v Pb acetate in the drinking water with or without A-type-EGCG-dimer coadministration (200 mg/kg body weight/day, intragastrically) for three months...
October 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29097114/endoplasmic-reticulum-stress-mediated-autophagy-activation-attenuates-fumonisin-b1-induced-hepatotoxicity-in-vitro-and-in-vivo
#5
Mahendra Pal Singh, Sun Chul Kang
Although pathological characteristics of fumonisin B1 are known to induce hepatic injury over prolonged periods, the cellular defense mechanisms against the detrimental effects of FB1 are still unknown. The underlying mechanisms of FB1 toxicity are thought to be related with the inhibition of ceramide synthase, causing an accumulation of sphingoid bases, which in turn cause development of oxidative stress. Herein, we investigated whether autophagy, a cellular defense mechanism, protects liver cells from FB1 exposure...
October 31, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29093014/irs-posttranslational-modifications-in-regulating-insulin-signaling
#6
Jinghua Peng, Ling He
Insulin resistance is the hallmark of type 2 diabetes; however, the mechanism underlying the development of insulin resistance is still not completely understood. Previous reports showed that posttranslational modifications of IRS play a critical role in insulin signaling, especially the phosphorylation of IRS by distinct kinases. While it is known that increasing Sirtuin 1 deacetylase activity improves insulin sensitivity in the liver, the identity of its counterpart, an acetyl-transferase, remains unknown...
November 1, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29074489/autophagy-and-the-unfolded-protein-response-promote-pro-fibrotic-effects-of-tgf%C3%AE-1-in-human-lung-fibroblasts
#7
Saeid Ghavami, Behzad Yeganeh, Amir A Zeki, Shahla Shojaei, Nicholas J Kenyon, Sean Ott, Afshin Samali, John Patterson, Javad Alizadeh, Adel Rezaei Moghadam, Ian M C Dixon, Helmut Unruh, Darryl A Knight, Martin Post, Thomas Klonisch, Andrew John Halayko
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease in adults with limited treatment options. Autophagy and the unfolded protein response (UPR), fundamental processes induced by cell stress, are dysregulated in lung fibroblasts and epithelial cells from humans with IPF. METHODS: Human primary cultured lung parenchymal and airway fibroblasts from non-IPF and IPF donors were stimulated with TGFβ1 with or without the inhibitors of autophagy or UPR (IRE1α inhibitor)...
October 26, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29044123/ire1%C3%AE-xbp1s-branch-of-upr-links-hif1%C3%AE-activation-to-mediate-angii-dependent-endothelial-dysfunction-under-particulate-matter-pm-2-5-exposure
#8
Xiuduan Xu, Aodeng Qimuge, Hongli Wang, Chen Xing, Ye Gu, Shasha Liu, Huan Xu, Meiru Hu, Lun Song
Short- and long-term exposure to particulate matter (PM) 2.5 instigates adverse health effect upon the cardiovascular (CV) system. Disclosing the molecular events by which PM2.5 evokes CV injuries is essential in developing effective risk-reduction strategy. Here we found that rats after intratracheally instillation with PM2.5 displayed increased circulating level of ANGII, the major bioactive peptide in renin-angiotensin-system (RAS), which resulted from the elevation of ANGII production in the vascular endothelium...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29027919/shiga-toxins-induce-apoptosis-and-er-stress-in-human-retinal-pigment-epithelial-cells
#9
Jun-Young Park, Yu-Jin Jeong, Sung-Kyun Park, Sung-Jin Yoon, Song Choi, Dae Gwin Jeong, Su Wol Chung, Byung Joo Lee, Jeong Hun Kim, Vernon L Tesh, Moo-Seung Lee, Young-Jun Park
Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are the most potent known virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications such as acute renal failure, blindness and neurological abnormalities. Although numerous studies have defined apoptotic responses to Shiga toxin type 1 (Stx1) or Shiga toxin type 2 (Stx2) in a variety of cell types, the potential significance of Stx-induced apoptosis of photoreceptor and pigmented cells of the eye following intoxication is unknown...
October 13, 2017: Toxins
https://www.readbyqxmd.com/read/29024602/knockdown-of-cemip-suppresses-proliferation-and-induces-apoptosis-in-colorectal-cancer-cells-downregulation-of-grp78-and-attenuation-of-unfolded-protein-response
#10
Guodong Liang, Xuedong Fang, Yubo Yang, Yan Song
Cell migration inducing hyaluronan binding protein (CEMIP) has been suggested as a contributor in the carcinogenesis of colorectal cancer (CRC). Cancer cells can adapt to endoplasmic reticulum (ER) stress by initiating unfolded protein response (UPR). This study aimed at investigating whether CEMIP affected the UPR of CRC cells, with a focus on 78 kDa glucose-regulated protein (GRP78, a major ER chaperone). We found that knockdown of CEMIP inhibited cell proliferation and induced a G1 arrest in SW480 CRC cells...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28992619/endoplasmic-reticulum-stress-induces-hrd1-to-protect-alveolar-type-ii-epithelial-cells-from-apoptosis-induced-by-cigarette-smoke-extract
#11
Shuang-Xiang Tan, Di-Xuan Jiang, Rui-Cheng Hu, Ai-Guo Dai, Gui-Xiang Gan, Dai-Yan Fu, Chun-Chu Kong, Yun-Rong Chen, Li-Le Wang, Jie Li
BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages...
October 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28971800/an-unfolded-protein-induced-conformational-switch-activates-mammalian-ire1
#12
Gülsün Elif Karagöz, Diego Acosta-Alvear, Hieu T Nguyen, Crystal P Lee, Feixia Chu, Peter Walter
The unfolded protein response (UPR) adjusts the cell's protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α's ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD's MHC-like groove and induce allosteric changes that lead to its oligomerization...
October 3, 2017: ELife
https://www.readbyqxmd.com/read/28959203/endoplasmic-reticulum-stress-mediates-methamphetamine-induced-blood-brain-barrier-damage
#13
Xiaojuan Qie, Di Wen, Hongyan Guo, Guanjie Xu, Shuai Liu, Qianchao Shen, Yi Liu, Wenfang Zhang, Bin Cong, Chunling Ma
Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood-brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28952924/unfolded-protein-response-transducer-ire1-mediated-signaling-independent-of-xbp1-mrna-splicing-is-not-required-for-growth-and-development-of-medaka-fish
#14
Tokiro Ishikawa, Makoto Kashima, Atsushi J Nagano, Tomoko Ishikawa-Fujiwara, Yasuhiro Kamei, Takeshi Todo, Kazutoshi Mori
When activated by the accumulation of unfolded proteins in the endoplasmic reticulum, metazoan IRE1, the most evolutionarily conserved unfolded protein response (UPR) transducer, initiates unconventional splicing of XBP1 mRNA. Unspliced and spliced mRNA are translated to produce pXBP1(U) and pXBP1(S), respectively. pXBP1(S) functions as a potent transcription factor, whereas pXBP1(U) targets pXBP1(S) to degradation. In addition, activated IRE1 transmits two signaling outputs independent of XBP1, namely activation of the JNK pathway, which is initiated by binding of the adaptor TRAF2 to phosphorylated IRE1, and regulated IRE1-dependent decay (RIDD) of various mRNAs in a relatively nonspecific manner...
September 27, 2017: ELife
https://www.readbyqxmd.com/read/28949381/autophagy-mediated-by-endoplasmic-reticulum-stress-enhances-the-caffeine-induced-apoptosis-of-hepatic-stellate-cells
#15
Yongjian Li, Yunyang Chen, Haiyan Huang, Minmin Shi, Weiping Yang, Jie Kuang, Jiqi Yan
Caffeine has been identified to have beneficial effects against chronic liver diseases, particularly liver fibrosis. Many studies have reported that caffeine ameliorates liver fibrosis by directly inducing hepatic stellate cell (HSC) apoptosis; however, the molecular mechanisms involved in this process remain unclear. The presents study aimed to detect the underlying mechanisms by which caffeine mediates HSC apoptosis and eliminates activated HSCs. For this purpose, the LX-2 cell line was applied in this study and the cells were exposed to various concentrations of caffeine for the indicated times...
September 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28945192/regulated-ire1-dependent-mrna-decay-requires-no-go-mrna-degradation-to-maintain-endoplasmic-reticulum-homeostasis-in-s-pombe
#16
Nicholas R Guydosh, Philipp Kimmig, Peter Walter, Rachel Green
The unfolded protein response (UPR) monitors and adjusts the protein folding capacity of the endoplasmic reticulum (ER). In S. pombe, the ER membrane-resident kinase/endoribonuclease Ire1 utilizes a mechanism of selective degradation of ER-bound mRNAs (RIDD) to maintain homeostasis. We used a genetic screen to identify factors critical to the Ire1-mediated UPR and found several proteins, Dom34, Hbs1 and Ski complex subunits, previously implicated in ribosome rescue and mRNA no-go-decay (NGD). Ribosome profiling in ER-stressed cells lacking these factors revealed that Ire1-mediated cleavage of ER-associated mRNAs results in ribosome stalling and mRNA degradation...
September 25, 2017: ELife
https://www.readbyqxmd.com/read/28939899/gpnmb-induces-bip-expression-by-enhancing-splicing-of-bip-pre-mrna-during-the-endoplasmic-reticulum-stress-response
#17
Yasuhiro Noda, Kazuhiro Tsuruma, Masafumi Takata, Mitsue Ishisaka, Hirotaka Tanaka, Yusuke Nakano, Yuki Nagahara, Masamitsu Shimazawa, Hideaki Hara
Glycoprotein nonmetastatic melanoma protein B (GPNMB) has a neuroprotective effect against neuronal cell death caused by the accumulation of abnormal mutated proteins. It is known that the accumulation of pathological proteins induces endoplasmic-reticulum (ER) stress leading to cell damage. The aim of this study was to determine the role of GPNMB in the ER stress response. GPNMB was greatly up-regulated by thapsigargin-induced ER stress. Under the ER stress conditions, GPNMB relocated to the nucleus and specifically up-regulated expression of BiP at the mRNA level by promoting the BiP pre-mRNA splicing, not through the pathways initiated by the three major transducers of the unfolded protein response: IRE1, PERK, and ATF6...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28933787/blocking-autophagy-enhances-the-apoptotic-effect-of-18%C3%AE-glycyrrhetinic-acid-on-human-sarcoma-cells-via-endoplasmic-reticulum-stress-and-jnk-activation
#18
Shuying Shen, Menglu Zhou, Kangmao Huang, Yizheng Wu, Yan Ma, Jiying Wang, Jianjun Ma, Shunwu Fan
Sarcoma, a rare form of cancer, is unlike the much more common carcinomas as it occurs in a distinct type of tissue. The potent antitumor effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, have been demonstrated in various cancers. However, the effect of GA on human sarcoma, and the underlying mechanisms, remain to be elucidated. In the current study, we show that GA inhibits sarcoma cell proliferation by inducing G0/G1-phase arrest. Exposure to GA resulted in the activation of caspase-3, -8, and -9, indicating that GA induced apoptosis through both extrinsic and intrinsic pathways...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28929238/nuclease-integrated-kinase-super-assemblies-niks-and-their-role-in-rna-processing
#19
REVIEW
Monica C Pillon, Robin E Stanley
Here we highlight the Grc3/Las1 complex, an essential RNA processing machine that is well conserved across eukaryotes and required for processing the pre-ribosomal RNA (pre-rRNA). Las1 is an endoribonuclease that cleaves the pre-rRNA while Grc3 is a polynucleotide kinase that phosphorylates the Las1-cleaved RNA product. Recently we showed that Grc3 and Las1 assemble into a higher-order complex composed of a dimer of Grc3/Las1 heterodimers that is required for nuclease and kinase activity. Unexpectedly, we found that the Grc3/Las1 complex draws numerous parallels with two other eukaryotic nucleases, Ire1 and RNase L...
September 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28929194/adapting-secretory-proteostasis-and-function-through-the-unfolded-protein-response
#20
Madeline Y Wong, Andrew S DiChiara, Patreece H Suen, Kenny Chen, Ngoc-Duc Doan, Matthew D Shoulders
Cells address challenges to protein folding in the secretory pathway by engaging endoplasmic reticulum (ER)-localized protective mechanisms that are collectively termed the unfolded protein response (UPR). By the action of the transmembrane signal transducers IRE1, PERK, and ATF6, the UPR induces networks of genes whose products alleviate the burden of protein misfolding. The UPR also plays instructive roles in cell differentiation and development, aids in the response to pathogens, and coordinates the output of professional secretory cells...
September 20, 2017: Current Topics in Microbiology and Immunology
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