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https://www.readbyqxmd.com/read/28923079/endoplasmic-reticulum-stress-cooperates-with-toll-like-receptor-ligation-in-driving-activation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#1
Pawel A Kabala, Chiara Angiolilli, Nataliya Yeremenko, Aleksander M Grabiec, Barbara Giovannone, Desiree Pots, Timothy R Radstake, Dominique Baeten, Kris A Reedquist
BACKGROUND: Endoplasmic reticulum (ER) stress has proinflammatory properties, and transgenic animal studies of rheumatoid arthritis (RA) indicate its relevance in the process of joint destruction. Because currently available studies are focused primarily on myeloid cells, we assessed how ER stress might affect the inflammatory responses of stromal cells in RA. METHODS: ER stress was induced in RA fibroblast-like synoviocytes (FLS), dermal fibroblasts, and macrophages with thapsigargin or tunicamycin alone or in combination with Toll-like receptor (TLR) ligands, and gene expression and messenger RNA (mRNA) stability was measured by quantitative polymerase chain reaction...
September 18, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28904818/nf-%C3%AE%C2%BAb-pathway-link-with-er-stress-induced-autophagy-and-apoptosis-in-cervical-tumor-cells
#2
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28890335/the-er-localized-transmembrane-protein-epg-3-vmp1-regulates-serca-activity-to-control-er-isolation-membrane-contacts-for-autophagosome-formation
#3
Yan G Zhao, Yong Chen, Guangyan Miao, Hongyu Zhao, Wenyan Qu, Dongfang Li, Zheng Wang, Nan Liu, Lin Li, She Chen, Pingsheng Liu, Du Feng, Hong Zhang
During autophagosome formation in mammalian cells, isolation membranes (IMs; autophagosome precursors) dynamically contact the ER. Here, we demonstrated that the ER-localized metazoan-specific autophagy protein EPG-3/VMP1 controls ER-IM contacts. Loss of VMP1 causes stable association of IMs with the ER, thus blocking autophagosome formation. Interaction of WIPI2 with the ULK1/FIP200 complex and PI(3)P contributes to the formation of ER-IM contacts, and these interactions are enhanced by VMP1 depletion. VMP1 controls contact formation by promoting SERCA (sarco[endo]plasmic reticulum calcium ATPase) activity...
September 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28887310/histone-deacetylase-6-inhibition-reduces-cysts-by-decreasing-via-camp-and-ca2-in-knockout-mouse-models-of-polycystic-kidney-disease
#4
Murali K Yanda, Qiangni Liu, Valeriu Cebotaru, William B Guggino, Liudmila Cebotaru
Autosomal dominant polycystic kidney disease (ADPKD) is associated with progressive en-largement of multiple renal cysts, often leading to renal failure which cannot be prevented by an current treatment. Two proteins encoded by two genes are associated with ADPKD, PC1 (pkd1), primarily a signaling molecule, and PC2 (pkd2), a Ca2+ channel. Dysregulation of cAMP signaling is central to ADPKD but the molecular mechanism is unresolved. Here we studied the role of histone deacetylase 6 (HDAC6) in regulating cyst growth to test the possibility that in-hibiting HDAC6 might help manage ADPKD...
September 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28884444/the-ccaat-box-in-the-proximal-serca2-gene-promoter-regulates-basal-and-stress-induced-transcription-in-cardiomyocytes
#5
Jorge Fragoso-Medina, Gabriela Rodriguez, Angel Zarain-Herzberg
The cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated...
September 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28883502/activation-of-endoplasmic-reticulum-stress-in-granulosa-cells-from-patients-with-polycystic-ovary-syndrome-contributes-to-ovarian-fibrosis
#6
Nozomi Takahashi, Miyuki Harada, Yasushi Hirota, Emi Nose, Jerilee Mk Azhary, Hiroshi Koike, Chisato Kunitomi, Osamu Yoshino, Gentaro Izumi, Tetsuya Hirata, Kaori Koga, Osamu Wada-Hiraike, R Jeffrey Chang, Shunichi Shimasaki, Tomoyuki Fujii, Yutaka Osuga
Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28866365/store-operated-calcium-entry-is-dispensable-for-the-activation-of-erk1-2-pathway-in-prostate-cancer-cells
#7
Aida M Lopez-Guerrero, Carlos Pascual-Caro, Francisco Javier Martin-Romero, Eulalia Pozo-Guisado
STIM1, the endoplasmic reticulum Ca(2+) sensor that modulates the activity of plasma membrane Ca(2+) channels, becomes phosphorylated at ERK1/2 target sites during Ca(2+) store depletion triggered by thapsigargin or epidermal growth factor (EGF). This ERK1/2-dependent phosphorylation regulates STIM1 localization and dissociation from microtubules, and it is known that enhances the binding to ORAI1, a store-operated Ca(2+) entry (SOCE) channel, leading to the activation of this Ca(2+) influx pathway. However, there remained some evidence of a role for SOCE in the activation of ERK1/2, and here we assessed the contribution of SOCE to ERK1/2 activation by generating a STIM1-deficient cell line by CRISPR/Cas9 genome editing of the STIM1 locus in prostate cancer PC3 cells...
August 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28865055/polychlorinated-biphenyl-19-blocks-the-most-common-form-of-store-operated-ca-2-entry-through-orai
#8
Keimin Lee, Yoon-Jung Kim, Yoon Young Cho, Sungkwon Chung, Su-Hyun Jo, Se-Young Choi
PCB19, a 2,2',6-trichlorinated biphenyl, is one of many non-dioxin-like polychlorinated biphenyls (NDL-PCBs), which are ubiquitous pollutants. NDL-PCBs affect cytosolic Ca(2+) signaling by promoting Ca(2+) release from ryanodine receptor-sensitive Ca(2+) pools and inhibiting store-operated Ca(2+) entry (SOCE) from the extracellular space. However, NDL-PCB-mediated SOCE inhibition has only been demonstrated in PC12 cells, in which SOCE is thought to be mainly mediated by TRPC family channels. Here, we investigated the effect of PCB19 on SOCE using human embryonic kidney 293 (HEK293) cells, human leukemia T cell line Jurkat-T cells and human promyelocytoma HL-60 cells which are the cell lines that are previously demonstrated to mediate the most common form of SOCE solely by the intrinsic Orai channels...
September 1, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28864210/inhibition-of-the-mevalonate-pathway-by-simvastatin-interferes-with-mast-cell-degranulation-by-disrupting-the-interaction-between-rab27a-and-double-c2-alpha-proteins
#9
Muhammad Novrizal Abdi Sahid, Shuang Liu, Takeshi Kiyoi, Kazutaka Maeyama
Statins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which block the mevalonate pathway. The activity of statins not only decreases cholesterol levels but also ameliorates inflammation and modulates the immune system. In this study, we investigated the effects of simvastatin on histamine release using rat basophilic leukaemia (RBL-2H3) cells, and examined its interaction with proteins involved in the exocytosis process. Treatment with simvastatin for 24h inhibited histamine release in RBL-2H3 cells in a concentration-dependent manner after stimulation with dinitrophenylated bovine serum albumin (DNP-BSA, as an antigen), ionomycin (a calcium ion [Ca(2+)] ionophore), and thapsigargin (an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum)...
August 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28855109/the-vasorelaxant-effect-of-mitiglinide-via-activation-of-voltage-dependent-k-channels-and-serca-pump-in-aortic-smooth-muscle
#10
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
August 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/28844859/endoplasmic-reticulum-stress-restrains-hepatocyte-growth-factor-expression-in-hepatic-stellate-cells-and-rat-acute-liver-failure-model
#11
Yuting Liu, Xiongxiong Pan, Shu Li, Yue Yu, Jianliang Chen, Jie Yin, Guoqiang Li
The aim of this study was to test whether endoplasmic reticulum (ER) stress suppresses hepatocyte growth factor (HGF) expression in hepatic stellate cells (HSCs) and whether ER stress plays a role in alleviating d-Galactosamine and Lipopolysaccharide (D-GalN/LPS)-induced acute liver failure (ALF) by regulating HGF expression. Rat HSCs line HSC-T6 were treated with the ER stress inducers tunicamycin or thapsigargin, and ER stress inhibitors sodium 4-phenylbutyrate (4-PBA) or salubrinal, respectively. Recombinant lentivirus containing eukaryotic translation initiation factor 2α (eIf2α), named LV-eIf2α-shRNA-GFP was produced to block eIf2α activated by ER stress...
August 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28844112/reactive-oxygen-species-produced-by-a-photodynamic-effect-induced-calcium-signal-in-neurons-and-astrocytes
#12
Maria Neginskaya, Elena Berezhnaya, Anatoly B Uzdensky, Andrey Y Abramov
Photodynamic therapy (PDT) leads to production of reactive oxygen species (ROS) and cell destruction due to oxidative stress. We used photodynamic effect of photosensitizer radachlorin to unravel the effect of photo-induced oxidative stress on the calcium signal and lipid peroxidation in primary culture of cortical neurons and astrocytes using live cell imaging. We have found that irradiation in presence of 200 nM of radachlorin induces calcium signal in primary neurons and astrocytes. Photo-induced neuronal calcium signal depends on internal calcium stores as it was still observed in calcium-free medium and could be blocked by depletion of endoplasmic reticulum (ER) stores with inhibitor of sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) thapsigargin...
August 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28839431/hwangryunhaedok-tang-induces-the-depolarization-of-pacemaker-potentials-through-5-ht3-and-5-ht4-receptors-in-cultured-murine-small-intestine-interstitial-cells-of-cajal
#13
Hyun Jung Kim, Guem San Lee, Hyungwoo Kim, Byung Joo Kim
AIM: To investigate the effects of a water extract of Hwangryunhaedok-tang (HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal (ICCs). METHODS: We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an anti-c-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode (I = 0). All experiments were performed at 30 °C-32 °C...
August 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28834298/the-vasorelaxant-effect-of-anti-diabetic-drug-nateglinide-via-activation-of-voltage-dependent-k-channels-in-aortic-smooth-muscle
#14
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Hyoweon Bang, Il-Whan Choi, Sung Hun Na, Won Sun Park
AIMS: We investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)-induced pre-contracted aortic rings. METHODS: Arterial tone measurement was performed in aortic smooth muscle. RESULTS: The application of nateglinide induced vasorelaxation in a concentration-dependent manner. Pretreatment with the large conductance Ca(2+) -activated K(+) (BKCa ) channel inhibitor paxilline, the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) , and ATP-sensitive K(+) (KATP ) channel inhibitor glibenclamide, did not affect the vasorelaxant effect of nateglinide...
August 20, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28833755/tacrolimus-regulates-endoplasmic-reticulum-stress-mediated-osteoclastogenesis-and-inflammation-in-vitro-and-collagen-induced-arthritis-mouse-model
#15
Won-Seok Lee, Ji-Hyeon Jeong, Eun-Gyeong Lee, Yun Jung-Choi, Jin-Hee Kim, Hang-Rae Kim, Wan-Hee Yoo
Tacrolimus is an immunosuppressive drug that inhibits the release of inflammatory cytokines involved in rheumatoid arthritis development by blocking T cell activation. "Endoplasmic reticulum stress," an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, has been implicated in rheumatoid arthritis and other inflammatory and metabolic diseases. We aimed to investigate the effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation and elucidate the underlying mechanisms...
August 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28832690/development-of-a-fluorescent-reporter-system-for-monitoring-er-stress-in-chinese-hamster-ovary-cells-and-its-application-for-therapeutic-protein-production
#16
Gargi Roy, Shu Zhang, Lina Li, Eileen Higham, Herren Wu, Marcello Marelli, Michael A Bowen
Mammalian cell expression systems have become a workhorse for the production of biotherapeutic proteins. As such, there is an ever increasing demand for higher productivity from these expression platforms to reduce manufacturing costs. While great advances have been made in the optimization of culture conditions and cell line selection to improve productivity, protein mis-folding remains a common limitation to high levels of production of therapeutic proteins. Accumulation of mis- and unfolded protein in the endoplasmic reticulum (ER) causes ER stress and initiates the unfolded protein response (UPR) that results in an activation of protein folding machinery, translation attenuation in an effort to proper folding of the newly synthesized peptides or may even lead to apoptosis if the correct folding is not restored...
2017: PloS One
https://www.readbyqxmd.com/read/28832644/3-o-trans-p-coumaroyl-alphitolic-acid-a-triterpenoid-from-zizyphus-jujuba-leads-to-apoptotic-cell-death-in-human-leukemia-cells-through-reactive-oxygen-species-production-and-activation-of-the-unfolded-protein-response
#17
Yohei Mitsuhashi, Yukihiro Furusawa, Tadashi Aradate, Qing-Li Zhao, Rohan Moniruzzaman, Masahiko Kanamori, Kyo Noguchi, Takashi Kondo
3-O-trans-p-coumaroyl-alphitolic acid (3OTPCA), a triterpenoid isolated from the plant Zizyphus jujuba (ZJ), is known to be cytotoxic to cancer cells; however, the molecular mechanism underlying 3OTPCA-induced cell death remains unknown. Here, we provide novel evidence that 3OTPCA induces apoptotic cell death in human leukemia cells. We found that 3OPTCA induces DNA fragmentation within 24 h after treatment in U937 cells, which was also observed in other leukemia cell lines, including Molt-4 and Jurkat cells...
2017: PloS One
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#18
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28808300/pterostilbene-exerts-anticancer-activity-on-non-small-cell-lung-cancer-via-activating-endoplasmic-reticulum-stress
#19
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/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#20
Lisann Pelzl, Bhaeldin Elsir, Itishri Sahu, Rosi Bissinger, Yogesh Singh, Basma Sukkar, Sabina Honisch, Ludger Schoels, Mohamed Jemaà, Elisabeth Lang, Alexander Storch, Andreas Hermann, Christos Stournaras, Florian Lang
BACKGROUND: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. PI3K dependent signalling upregulates Orai1, a pore forming channel protein accomplishing store operated Ca2+ entry (SOCE)...
August 11, 2017: Cellular Physiology and Biochemistry
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