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thapsigargin

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https://www.readbyqxmd.com/read/28320096/a-natural-compound-jaceosidin-ameliorates-endoplasmic-reticulum-stress-and-insulin-resistance-via-upregulation-of-serca2b
#1
Zijun Ouyang, Wanshuai Li, Qianqian Meng, Qi Zhang, Xingqi Wang, Ahmed Elgehama, Xudong Wu, Yan Shen, Yang Sun, Xuefeng Wu, Qiang Xu
Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28315494/role-of-the-unfolded-protein-response-in-topography-induced-osteogenic-differentiation-in-rat-bone-marrow-mesenchymal-stem-cells
#2
Mengqi Shi, Wen Song, Tianxiao Han, Bei Chang, Guangwen Li, Jianfeng Jin, Yumei Zhang
The topography of biomaterials can significantly influence the osteogenic differentiation of cells. Understanding topographical signal transduction is critical for developing biofunctional surfaces, but the current knowledge is insufficient. Recently, numerous reports have suggested that the unfolded protein response (UPR) and osteogenic differentiation are inter-linked. Therefore, we hypothesize that the UPR pathway may be involved in the topography-induced osteogenesis. In the present study, different surface topographies were fabricated on pure titanium foils and the endoplasmic reticulum (ER) stress and UPR pathway were systematically investigated...
March 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#3
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- and milli-calpain. Upon the inhibition of the endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1 dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1 containing vesicles with LC3 bodies in control cells. On the opposite, CAPNS1 depletion is coupled to an accumulation of LC3 bodies and Rab5 early endosomes...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28299899/salivary-gland-hypofunction-in-kk-ay-type-2-diabetic-mice
#4
Takashi Munemasa, Taro Mukaibo, Yusuke Kondo, Chihiro Masaki, Yuichiro Kusuda, Yuta Miyagi, Shintaro Tsuka, Ryuji Hosokawa, Tetsuji Nakamoto
BACKGROUND: Diabetes mellitus induces several hypofunctions in the body, including in the oral cavity. It is often associated with xerostomia, however the detailed underlying mechanism is not well characterized. METHODS: We used KK-Ay mice, a model of type 2 diabetes, to analyze the mechanism of diabetes-induced xerostomia with the ex vivo glandular perfusion technique, histological analysis, immunohistochemically and intracellular signaling analysis. RESULTS: Ex vivo submandibular gland secretions from KK-Ay mice decreased by 30% when stimulated with moderate stimulation of cholinergic agonist 0...
March 16, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28285140/analysis-of-the-potency-of-various-low-molecular-weight-chemical-chaperones-to-prevent-protein-aggregation
#5
Chandak Upagupta, Rachel E Carlisle, Jeffrey G Dickhout
Newly translated proteins must undergo proper folding to ensure their function. To enter a low energy state, misfolded proteins form aggregates, which are associated with many degenerative diseases, such as Huntington's disease and chronic kidney disease (CKD). Recent studies have shown the use of low molecular weight chemical chaperones to be an effective method of reducing protein aggregation in various cell types. This study demonstrates a novel non-biased assay to assess the molecular efficacy of these compounds at preventing protein misfolding and/or aggregation...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28285135/a-novel-transmembrane-protein-defines-the-endoplasmic-reticulum-stress-induced-cell-death-pathway
#6
Tomoya Tamaki, Kenta Kamatsuka, Taku Sato, Shuntaro Morooka, Kosuke Otsuka, Masahiro Hattori, Tomoyasu Sugiyama
Mitochondrial membrane potential (ΔΨm) maintenance is physiologically critical in cells; its loss causes apoptotic signalling and cell death. Accumulating DNA mutations and unfolded proteins in stressed cells activate signalling pathways for cell death induction. Cancer cells often fail to die even in the presence of some death signalling proteins. Here, we report a short hairpin RNA (shRNA) with an artificial sequence, denoted Psi1 shRNA, which leads to ΔΨm loss in HCT116 cells. The Psi1 shRNA target gene was shown to encode transmembrane protein 117 (TMEM117)...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28280417/hydrogen-peroxide-attenuates-refilling-of-intracellular-calcium-store-in-mouse-pancreatic-acinar-cells
#7
Mi Na Yoon, Dong Kwan Kim, Se Hoon Kim, Hyung Seo Park
Intracellular calcium (Ca(2+)) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide (H2O2) on intracellular Ca(2+) accumulation in mouse pancreatic acinar cells. Perfusion of H2O2 at 300 µM resulted in additional elevation of intracellular Ca(2+) levels and termination of oscillatory Ca(2+) signals induced by carbamylcholine (CCh) in the presence of normal extracellular Ca(2+)...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28275147/localization-and-characterization-of-cyp76ae2-part-of-thapsigargin-biosynthesis-in-thapsia-garganica
#8
Trine Bundgaard Andersen, Karen Agatha Martinez-Swatson, Silas Anselm Rasmussen, Berin Alain Boughton, Kirsten Jørgensen, Johan Andersen-Ranberg, Nils Nyberg, Søren Brøgger Christensen, Henrik Toft Simonsen
The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as Deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the SERCA calcium pump in mammals, and is of industrial importance as the active moiety of the anticancer drug Mipsagargin, currently in clinical trials. Knowledge of thapsigargin in planta storage and biosynthesis has so far been limited. Here we present the putative second step in thapsigargin biosynthesis, by showing that the cytochrome P450 TgCYP76AE2, transiently expressed in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide...
March 8, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28274920/h2o2-augments-cytosolic-calcium-in-nucleus-tractus-solitarii-neurons-via-multiple-voltage-gated-calcium-channels
#9
Tim D Ostrowski, Heather A Dantzler, Luis Polo-Parada, David D Kline
Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28271591/a-novel-heterozygous-mutation-of-the-wfs1-gene-leading-to-constitutive-endoplasmic-reticulum-stress-is-the-cause-of-wolfram-syndrome
#10
Shuntaro Morikawa, Toshihiro Tajima, Akie Nakamura, Katsura Ishizu, Tadashi Ariga
BACKGROUND: Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms...
March 8, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28264934/structure-activity-relationship-of-thapsigargin-inhibition-on-the-purified-golgi-secretory-pathway-ca2-mn2-transport-atpase-spca1a
#11
Jialin Chen, Joren De Raeymaecker, Jannik Brøndsted Hovgaard, Susanne Smaardijk, Ilse Vandecaetsbeek, Frank Wuytack, Jesper Vuust Møller, Jan Eggermont, Marc De Maeyer, Søren Brøgger Christensen, Peter Vangheluwe
The Golgi/secretory pathway Ca2+/Mn2+ transport ATPase (SPCA1a) is implicated in breast cancer and Hailey-Hailey disease. Here, we purified recombinant human SPCA1a from Saccharomyces cerevisiae and measured Ca2+ dependent ATPase activity following reconstitution in proteoliposomes. The purified SPCA1a displays a higher apparent Ca2+ affinity and lower maximal turnover rate than the purified sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1a). The lipids cholesteryl hemisuccinate, linole-/oleamide and phosphatidyl ethanolamine inhibit, whereas phosphatidic acid and sphingomyelin enhance SPCA1a activity...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28260038/the-nerve-growth-factor-alters-calreticulin-translocation-from-the-endoplasmic-reticulum-to-the-cell-surface-and-its-signaling-pathway-in-epithelial-ovarian-cancer-cells
#12
Carolina Andrea Vera, Lorena Oróstica, Fernando Gabler, Arturo Ferreira, Alberto Selman, Margarita Vega, Carmen Aurora Romero
Ovarian cancer is the seventh most common cancer among women worldwide, causing approximately 120,000 deaths every year. Immunotherapy, designed to boost the body's natural defenses against cancer, appears to be a promising option against ovarian cancer. Calreticulin (CRT) is an endoplasmic reticulum (ER) resident chaperone that, translocated to the cell membrane after ER stress, allows cancer cells to be recognized by the immune system. The nerve growth factor (NGF) is a pro-angiogenic molecule overexpressed in this cancer...
February 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28256007/targeting-notch-activated-m1-macrophages-attenuates-joint-tissue-damage-in-a-mouse-model-of-inflammatory-arthritis
#13
Wen Sun, Hengwei Zhang, Hua Wang, Yahui Grace Chiu, Christopher T Ritchlin, Amy Kiernan, Brendan F Boyce, Lianping Xing
Expression of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP +) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker...
March 3, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28253590/-activation-of-endoplasmic-reticulum-stress-and-its-effect-on-osteogenic-differentiation-induced-by-micropit-nanotube-topography
#14
M Q Shi, W Song, T X Han, B Chang, Y M Zhang
Objective: To explore the activation of endoplasmic reticulum stress (ERS) in bone marrow mesenchymal stem cell (BMMSC) and its effect on osteogenic differentiation induced by micropit/nanotube topography (MNT), so as to provide guidance for the topography design of biomaterials. Methods: Four sample groups were fabricated: polishing control group (polished titanium, PT, no treatment), thapsigargin treatment (TG, 0.1 μmol/L TG treated for 9 h), MNT5 and MNT20 (anodized at 5 V and 20 V after acid etching). Scanning electron microscope (SEM) was used to observe the topography of Ti samples...
February 9, 2017: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/28252652/bh3-mimetic-elicited-ca-2-signals-in-pancreatic-acinar-cells-are-dependent-on-bax-and-can-be-reduced-by-ca-2-like-peptides
#15
Pawel E Ferdek, Monika A Jakubowska, Polina Nicolaou, Julia V Gerasimenko, Oleg V Gerasimenko, Ole H Petersen
BH3 mimetics are small-molecule inhibitors of B-cell lymphoma-2 (Bcl-2) and Bcl-xL, which disrupt the heterodimerisation of anti- and pro-apoptotic Bcl-2 family members sensitising cells to apoptotic death. These compounds have been developed as anti-cancer agents to counteract increased levels of Bcl-2 proteins often present in cancer cells. Application of a chemotherapeutic drug supported with a BH3 mimetic has the potential to overcome drug resistance in cancers overexpressing anti-apoptotic Bcl-2 proteins and thus increase the success rate of the treatment...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28249687/activation-of-endoplasmic-reticulum-calcium-leak-by-2-apb-depends-on-the-luminal-calcium-concentration
#16
Daniel Leon-Aparicio, Jesus Chavez-Reyes, Agustin Guerrero-Hernandez
It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca(2+) level ([Ca(2+)]ER) and we have carried out simultaneous recordings of both [Ca(2+)]i and the [Ca(2+)]ER in HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca(2+)]ER by activating an ER-resident Ca(2+) permeable channel more than by inhibiting the activity of SERCA pumps...
February 8, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#17
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28216898/depolarizing-effects-of-daikenchuto-on-interstitial-cells-of-cajal-from-mouse-small-intestine
#18
Hyungwoo Kim, Hyun Jung Kim, Dongki Yang, Myeong Ho Jung, Byung Joo Kim
BACKGROUND: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. OBJECTIVE: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28212796/sodium-calcium-exchanger-in-pig-coronary-artery
#19
A K Grover
This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na(+)-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca(2+) concentration and extracellular entry of (45)Ca(2+). All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca(2+) pump SERCA2b whose activity was much greater than that of NCX...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28211571/inhibitory-effects-of-a-standardized-extract-of-justicia-pectoralis-in-an-experimental-rat-model-of-airway-hyper-responsiveness
#20
Carlos T M Moura, Francisco J Batista-Lima, Teresinha S Brito, Alfredo A V Silva, Luan C Ferreira, Cássia R Roque, Karoline S Aragão, Alexandre Havt, Francisco N Fonseca, Luzia K A M Leal, Pedro J C Magalhães
OBJECTIVE: Justicia pectoralis is a plant useful for the treatment of respiratory diseases. Here, we studied the antiasthmatic properties of a standardized extract of J. pectoralis (Jp). METHODS: Ovalbumin (OVA)-sensitized rats were actively challenged with saline or OVA to study airway hyper-responsiveness after oral treatment with saline or Jp. The ability of Jp to inhibit hyper-reactivity was evaluated in isolated trachea mounted in isolated organ bath chamber...
February 17, 2017: Journal of Pharmacy and Pharmacology
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