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https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#1
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Sarka Lhotak, Pei Yu, Gabriel Gyulay, Guillaume Pare, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER localized transcription factor that directly upregulates sterol-regulatory genes, including PCSK9. Given that PCSK9 contributes to atherosclerosis by targeting low-density lipoprotein (LDL) receptor (LDLR) degradation, our present study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
December 1, 2016: Journal of Biological Chemistry
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
#2
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/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#3
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27886513/a-potential-role-for-endoplasmic-reticulum-stress-in-progesterone-deficiency-in-obese-women
#4
Nozomi Takahashi, Miyuki Harada, Yasushi Hirota, Lin Zhao, Jerilee Mk Azhary, Osamu Yoshino, Gentaro Izumi, Tetsuya Hirata, Kaori Koga, Osamu Wada-Hiraike, Tomoyuki Fujii, Yutaka Osuga
Obesity in reproductive-aged women is associated with shorter luteal phase and lower progesterone levels. Lipid accumulation in follicles of obese women compromises endoplasmic reticulum (ER) function, activating ER stress in granulosa cells. We hypothesized that ER stress activation in granulosa-lutein cells (GLCs) would modulate progesterone production and contribute to obesity-associated progesterone deficiency. Pretreatment with an ER stress inducer, tunicamycin or thapsigargin, inhibited human chorionic gonadotropin (hCG)-stimulated progesterone production in cultured human GLCs...
November 25, 2016: Endocrinology
https://www.readbyqxmd.com/read/27885588/a-mouse-model-reveals-that-mfsd2a-is-critical-for-unfolded-protein-response-upon-exposure-to-tunicamycin
#5
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/27881436/knockdown-of-histidine-rich-calcium-binding-protein-hrc-suppresses-liver-fibrosis-by-inhibiting-the-activation-of-hepatic-stellate-cells
#6
Jingmei Liu, Mengke Li, Jin Gong, Ping Han, Yunwu Wang, Dean Tian, Jiazhi Liao
The histidine-rich calcium binding protein (HRC) is a regulator of Ca(2+)- homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrated that HRC was upregulated in fibrotic liver and activated HSCs. TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagens expression, and inhibited HSCs proliferation and migration...
November 23, 2016: Biology Open
https://www.readbyqxmd.com/read/27879249/glucosamine-induces-er-stress-by-disrupting-lipid-linked-oligosaccharide-biosynthesis-and-n-linked-protein-glycosylation
#7
Daniel R Beriault, Vi T Dang, Lexy H Zhong, Christina I Petlura, Cameron S McAlpine, Yuanyuan Shi, Geoff H Werstuck
Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has been implicated in the development of diabetic complications including atherosclerosis and hepatic steatosis. In this study, we investigate the potential relationship between the effects of glucosamine on lipid linked oligosaccharide (LLO) biosynthesis, N-linked glycosylation, and ER homeostasis. Mouse embryonic fibroblasts (MEFs) were cultured in the presence of 0-5 mM glucosamine for up to 18 hours and LLO biosynthesis was monitored by fluorescence-assisted carbohydrate electrophoresis...
November 22, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27872020/niclosamide-ethanolamine-inhibits-artery-constriction
#8
Shan-Liang Li, Jie Yan, Yan-Qiu Zhang, Chang-Lin Zhen, Ming-Yu Liu, Jing Jin, Jin-Lai Gao, Xiao-Lin Xiao, Xin Shen, Yu Tai, Nan Hu, Xin-Zi Zhang, Zhi-Jie Sun, De-Li Dong
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system...
November 18, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#9
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27865417/knock-down-of-apoptosis-inducing-factor-gene-protects-endoplasmic-reticulum-stress-mediated-goat-granulosa-cell-apoptosis
#10
Diqi Yang, Tingting Jiang, Pengfei Lin, Huatao Chen, Lei Wang, Nan Wang, Fan Zhao, Aihua Wang, Yaping Jin
The apoptosis of granulosa cells is the main cause of follicular atresia, and endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa cells. Apoptosis inducing factor (AIF) mediates caspase-independent apoptosis and causes chromatin condensation and DNA fragmentation, but its role in ER stress-mediated granulosa cell apoptosis during goat follicular atresia remains largely unknown. The aim of this study was to investigate the function of AIF in the apoptosis of goat granulosa cells mediated by ER stress...
January 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/27826230/ampa-receptors-are-involved-in-store-operated-calcium-entry-and-interact-with-stim-proteins-in-rat-primary-cortical-neurons
#11
Joanna Gruszczynska-Biegala, Maria Sladowska, Jacek Kuznicki
The process of store-operated calcium entry (SOCE) leads to refilling the endoplasmic reticulum (ER) with calcium ions (Ca(2+)) after their release into the cytoplasm. Interactions between (ER)-located Ca(2+) sensors (stromal interaction molecule 1 [STIM1] and STIM2) and plasma membrane-located Ca(2+) channel-forming protein (Orai1) underlie SOCE and are well described in non-excitable cells. In neurons, however, SOCE appears to be more complex because of the importance of Ca(2+) influx via voltage-gated or ionotropic receptor-operated Ca(2+) channels...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27815070/direct-detection-of-serca-calcium-transport-and-small-molecule-inhibition-in-giant-unilamellar-vesicles
#12
Tengfei Bian, Joseph M Autry, Denise Casemore, Ji Li, David D Thomas, Gaohong He, Chengguo Xing
We have developed a charge-mediated fusion method to reconstitute the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in giant unilamellar vesicles (GUV). Intracellular Ca(2+) transport by SERCA controls key processes in human cells such as proliferation, signaling, and contraction. Small-molecule effectors of SERCA are urgently needed as therapeutics for Ca(2+) dysregulation in human diseases including cancer, diabetes, and heart failure. Here we report the development of a method for efficiently reconstituting SERCA in GUV, and we describe a streamlined protocol based on optimized parameters (e...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27813252/the-calcium-binding-protein-alg-2-promotes-er-exit-site-localization-and-polymerization-of-tfg
#13
Takashi Kanadome, Hideki Shibata, Keiko Kuwata, Terunao Takahara, Masatoshi Maki
ALG-2 (apoptosis-linked gene 2, a gene product of PDCD6) is a 22-kDa Ca(2+) -binding protein. Accumulating evidence points to a role for ALG-2 as a Ca(2+) -responsive adaptor protein. On binding to Ca(2+) , ALG-2 undergoes a conformational change that facilitates its interaction with various proteins. It also forms a homodimer and heterodimer with peflin, a paralog of ALG-2. However, the differences in cellular roles for the ALG-2 homodimer and ALG-2/peflin heterodimer are unclear. Here, we found that TFG (Trk-fused gene) interacted with the ALG-2 homodimer...
November 4, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27806939/functional-loss-of-dhrs7c-induces-intracellular-ca2-overload-and-myotube-enlargement-in-c2c12-cells-via-calpain-activation
#14
Shinobu Arai, Masataka Ikeda, Tomomi Ide, Yuka Matsuo, Takeo Fujino, Katsuya Hirano, Kenji Sunagawa, Hiroyuki Tsutsui
Dehydrogenase/reductase member 7C (DHRS7C) is a newly identified NAD/NADH-dependent dehydrogenase that is expressed in cardiac and skeletal muscle and localized in the endoplasmic/sarcoplasmic reticulum (ER/SR). However, its functional role in muscle cells remains to be fully elucidated. Here, we investigated the role of DHRS7C by analyzing mouse C2C12 myoblasts deficient in DHRS7C (DHRS7C-KO cells), overexpressing wild-type DHRS7C (DHRS7C-WT cells), or expressing mutant DHRS7C (DHRS7C-Y191F or DHRS7C-K195Q cells, harboring point mutations in the NAD/NADH-dependent dehydrogenase catalytic core domain [YXXXK])...
November 2, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27795806/c1q-tnf-related-protein-9-protects-diabetic-rat-heart-against-ischemia-reperfusion-injury-role-of-endoplasmic-reticulum-stress
#15
Sanxing Bai, Liang Cheng, Yang Yang, Chongxi Fan, Dajun Zhao, Zhigang Qin, Xiao Feng, Lin Zhao, Jipeng Ma, Xiaowu Wang, Jian Yang, Xuezeng Xu, Dinghua Yi, Wei Yi
As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-α expression, and lactate dehydrogenase activity...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27790936/effect-of-protriptyline-on-ca-2-i-and-viability-in-mg63-human-osteosarcoma-cells
#16
Ching-Kai Su, Chiang-Ting Chou, Ko-Long Lin, Wei-Zhe Liang, Jin-Shiung Cheng, Hong-Tai Chang, I-Shu Chen, Ti Lu, Chun-Chi Kuo, Chia-Cheng Yu, Pochuen Shieh, Daih-Huang Kuo, Fu-An Chen, Chung-Ren Jan
Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca(2+ )concentrations ([Ca(2+)]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca(2+)]i rises concentration-dependently...
October 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27783653/humanin-protects-rpe-cells-from-endoplasmic-reticulum-stress-induced-apoptosis-by-upregulation-of-mitochondrial-glutathione
#17
Douglas Matsunaga, Parameswaran G Sreekumar, Keijiro Ishikawa, Hiroto Terasaki, Ernesto Barron, Pinchas Cohen, Ram Kannan, David R Hinton
Humanin (HN) is a small mitochondrial-encoded peptide with neuroprotective properties. We have recently shown protection of retinal pigmented epithelium (RPE) cells by HN in oxidative stress; however, the effect of HN on endoplasmic reticulum (ER) stress has not been evaluated in any cell type. Our aim here was to study the effect of HN on ER stress-induced apoptosis in RPE cells with a specific focus on ER-mitochondrial cross-talk. Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL)...
2016: PloS One
https://www.readbyqxmd.com/read/27778132/insights-on-the-involvement-of-epigallocatechin-gallate-in-er-stress-mediated-apoptosis-in-age-related-macular-degeneration
#18
Bose Karthikeyan, Lakshminarasimhan Harini, Vaithilingam Krishnakumar, Velu Rajesh Kannan, Krishnan Sundar, Thandavarayan Kathiresan
Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H2O2) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells...
October 24, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27777379/impaired-autophagy-activity-is-linked-to-elevated-er-stress-and-inflammation-in-aging-adipose-tissue
#19
Amiya Kumar Ghosh, Theresa Mau, Martin O'Brien, Sanjay Garg, Raymond Yung
Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort...
October 24, 2016: Aging
https://www.readbyqxmd.com/read/27769892/bimodal-modulation-of-store-operated-ca-2-channels-by-clozapine-in-astrocytes
#20
Yuzuki Kanda, Miho Okada, Rina Ikarashi, Eri Morioka, Takashi Kondo, Masayuki Ikeda
Clozapine (Clz) and olanzapine (Olz) are second generation (atypical) antipsychotics, used widely for treating schizophrenia and bipolar disorder. These drugs share multiple sites of actions, however their mechanisms remain incompletely understood. Here, we analyzed the effects of these drugs on primary cultures of rat cortical astrocytes and C6 glioma cells using fura-2-based Ca(2+) imaging. C6 cells, but not cortical astrocytes, express the serotonin 2A receptor subtype, which couples to phospholipase C. Clz (1μM) significantly blocked serotonin-induced Ca(2+) transients in C6 cells, consistent with known antagonistic actions of Clz...
December 2, 2016: Neuroscience Letters
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