• Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
  • Activity Thapsigargin is an extremely tight-binding inhibitor of intracellular Ca 2+ pumps, but initially described as a tumor promoting agent which induces rapid Ca 2+ release from intracellular stores 1 . (alomone.com)
  • Thapsigargin , derived from the plant genus Thapsia 1,2 , is an extremely tight-binding inhibitor of intracellular Ca 2+ pumps. (alomone.com)
  • 0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. (ed.ac.uk)
  • 0.05), whereas 1 M thapsigargin [SERCA inhibitor (15)] decreased uptake even further ( (brinda.info)
  • Chelation of extracellular Ca2+ by EGTA efficiently abrogated the thapsigargin- or CPA-induced pErk response, demonstrating the strong Erk activation observed in the Stim1-overexpressing DT40 cells is due to the increased IDH1 Inhibitor 2 SOCE in these cells. (mdm-inhibitors.com)
  • We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. (johnshopkins.edu)
  • Diclofenac significantly suppressed SH-SY5Y cell death induced by two types of ER-stress-inducing agents: thapsigargin, an inhibitor of Ca 2+ -ATPase on the endoplasmic reticulum membrane, and tunicamycin, a glycosylation blocker. (elsevierpure.com)
  • Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
  • These data indicate that in human ASM, SERCA is regulated by mechanisms such as CaMKII and that airway inflammation maintains [Ca2+]i levels by decreasing SERCA expression and slowing Ca2+ reuptake. (brinda.info)
  • SERCA inhibition by thapsigargin was used as a control for inhibited reuptake. (brinda.info)
  • Thapsigargin and CPA result in SOCE by inhibiting the SERCA pumps in the ER, thereby inducing passive launch of Ca2+ from your ER stores while bypassing proximal BCR signaling. (mdm-inhibitors.com)
  • The present study investigated the effects of GSK2606414 on proliferation, apoptosis, and the expression of activating transcription factor 4 (ATF4), CCAAT/enhancer‑binding protein homologous protein (CHOP) and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under endoplasmic reticulum (ER) stress. (spandidos-publications.com)
  • Disruption of PERK activity has been demonstrated to reduce hydroquinone-induced apoptosis and hypoxia-induced VEGF expression in human RPE cells in vitro ( 5 , 21 ). (spandidos-publications.com)
  • Thapsigargin-induced depletion of Ca 2+ stores causes apoptosis in most cell lines 5 . (alomone.com)
  • Consistent with a role for Ca2+ in antigen-induced apoptosis8, 10, Stim1 overexpression sensitized DT40 cells to both BCR- and thapsigargin-induced apoptosis (Fig. 1b). (mdm-inhibitors.com)
  • Open in a separate window Physique 1 Sensitization of B cells to antigen-induced apoptosis correlates with Ca2+- dependent Erk activation(a) Intracellular Ca2+ measurements following activation with 1 M thapsigargin or the anti-BCR antibody M4. (mdm-inhibitors.com)
  • Indeed expression of a dominant-negative form of CREB (KCREB) in metastatic melanoma cells sensitizes them to thapsigargin-induced apoptosis (12). (antiviralbiologic.com)
  • In an analogous manner intracellular expression of an inhibitory anti-ATF-1 single chain variable fragment (ScFv) antibody in MeWo melanoma cells suppresses their tumorigenicity and metastatic potential in nude mice (21 22 Expression of ScFv anti-ATF-1 renders the melanoma cells susceptible to thapsigargin-induced apoptosis and causes massive apoptosis in tumors transplanted subcutaneously into nude mice (23). (antiviralbiologic.com)
  • The aim of this study is to examine the involvement of NSAIDs, in particular diclofenac, on ER-stress-induced apoptosis of human neuroblastoma SH-SY5Y cells. (elsevierpure.com)
  • Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. (wikipedia.org)
  • Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion. (wikipedia.org)
  • Herein we report that DCPA attenuates the normal elevated and sustained [Ca2+](i) that follows internal store depletion in the human leukemic Jurkat T cell line and primary mouse T cells. (cdc.gov)
  • DCPA did not alter the depletion of internal Ca2+ stores when stimulated by anti-CD3 or thapsigargin demonstrating that early inositol 1,4,5-triphosphate-mediated signaling and depletion of Ca2+ stores were unaffected. (cdc.gov)
  • Exposure of Jurkat cells to either DCPA or 50 mu M 2-APB attenuated the increase in [Ca2+](i) following thapsigargin or anti-CD3 induced store depletion in a similar manner. (cdc.gov)
  • We showed that passive endoplasmic reticulum (ER) depletion by thapsigargin or cell stimulation by histamine activated a similar Ca(2+)-release-activated Ca(2+) current (CRAC)-like current when 10 mM Ba(2+)/2 mM Ca(2+) was present in the extracellular solution. (unige.ch)
  • To better understand the mechanisms of CREB-induced tumor growth and metastasis and identify other proteins/factors involved in CREB-induced tumor growth and metastasis we silenced CREB expression by stably transfecting the highly metastatic human melanoma cell lines A375SM and C8161-c9 with a lentivirus-based short hairpin RNA (shRNA). (antiviralbiologic.com)
  • G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. (johnshopkins.edu)
  • Instead, we found that ADAM17 induction by severe hypoxia can be mimicked by ER stressors such as Thapsigargin and occurs as a consequence of the activation of the PERK/eIF2α/ATF4 and activating transcription factor 6 (ATF6) arms of UPR in several tumor cell lines. (ox.ac.uk)
  • Preclinical studies demonstrated that other effects of thapsigargin include suppression of nicotinic acetylcholine receptors activity in neurons of the guinea-pig ileum submucous plexus and rat superior cervical ganglion. (wikipedia.org)
  • We developed a calcium signaling-based assay, using cultured human embryonic kidney cells (HEK), that evaluates simultaneously, the activation/desensitization or blockade of the proteinase-activated receptors, PAR 1 and PAR 2 . (aspetjournals.org)
  • Surprisingly, no PLB expression was detected in either lysates of enzymatically dissociated human ASM cells or in tissue homogenates of human bronchi (Fig. 2), in spite of the mRNA present. (brinda.info)
  • d) Phosphotyrosine-containing proteins were immunoprecipitated with the 4G10 antibody from lysates of thapsigargin-stimulated Stim1-overexpressing DT40 cells. (mdm-inhibitors.com)
  • Quantitative RT-PCR revealed that PLB mRNA is present in human ASM (Fig. 1). (brinda.info)
  • RESULTS PLB protein is not detectable in human ASM. (brinda.info)
  • To verify that the protein content in the gel electrophoresis was not a limiting factor, in some experiments, 100 g of human bronchial homogenate was loaded, with no PLB detectable even under these conditions (data not shown). (brinda.info)
  • Increased SOCE leads to Ca2+-dependent Erk activation We examined the phosphotyrosine profile of Stim1-overexpressing DT40 B cells following thapsigargin activation for 2 and 5 minutes and observed robust and continual tyrosine phosphorylation of a ~42 kDa band, which was only modestly detectable in thapsigargin-stimulated wild-type DT40 cells (Fig. 1c). (mdm-inhibitors.com)
  • In cultured human cells or bronchial organoids, these SASR-CoV-2 infection-induced senescent cells express high levels of a series of inflammatory factors known as senescence-associated secretory phenotypes (SASPs)4 in a sustained manner, even after SARS-CoV-2 is no longer detectable. (bvsalud.org)
  • Our data support a role of fortilin in the unfolded protein response and its potential participation in human diseases caused by unfolded proteins response. (ampkpathway.com)
  • qPCR revealed that the other observed UPR markers were activated as well upon thapsigargin treatment, however, they were not decreased with the treatment with IRE1 specific inhibitors. (helsinki.fi)
  • To this end, we developed a calcium-signaling assay, employing cultured human embryonic kidney cells (HEK293) in which the action of PAR 1 and PAR 2 agonists and antagonists could be evaluated simultaneously. (aspetjournals.org)
  • These results show that calcium-mobilizing GPCR agonists functionally interact with TNF-α to differentially regulate pro-inflammatory genes expression in human ASM cells, possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC. (tmu.edu.tw)
  • Melatonin induces reactive oxygen species generation and changes in glutathione levels and reduces viability in human pancreatic stellate cells. (crcm-marseille.fr)
  • Here we show that direct elevation of cytoplasmic Ca 2+ by extracellular application of a low concentration of ryanodine, which activated Ca 2+ release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. (jneurosci.org)
  • Bacterial effects on in vitro mineralization of human periodontal fibroblasts (HPF) have not yet been examined in great detail. (go.jp)
  • Firstly, the translocation of mature CLU from the ER/Golgi into the cytosol of human astrocytoma U251 cells in response to ER stress was shown by two complementary biochemical and immunofluorescence approaches [ 15 ]. (biomedcentral.com)
  • Subsequently it was demonstrated that the ER-resident chaperone BiP (GRP78) facilitates the translocation of CLU to the cytosol during ER stress in human prostate cancer LNCaP cells [ 16 ]. (biomedcentral.com)
  • Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
  • Using thapsigargin (Tg), an agent that mobilizes calcium by directly emptying intracellular stores, we previously showed that intracellular calcium may play an important role in the regulation of intercellular adhesion molecule (ICAM)-1 gene expression induced by cytokines in human airway smooth muscle (ASM) cells. (tmu.edu.tw)
  • The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter. (e-dmj.org)
  • ARPE‑19 human RPE cells were treated with 0.01‑50 µM GSK2606414, and ER stress was induced by thapsigargin (TG) treatment. (spandidos-publications.com)
  • In order to study the regulation or IRE1 branch of the UPR, and to identify the ER-stress-modulating compounds, a human luciferase reporter cell line (XBP1-NLuc) was created in this work. (helsinki.fi)
  • We also showed that in Drosophila photoreceptor cells, clusterin co-expression gave ER stress-dependent protection against proteotoxicity arising from both Huntingtin-Q128 and mutant (R406W) human tau. (biomedcentral.com)
  • In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of protein synthesis is observed only in cells infected with gamma(1)z34.5- mutants. (scienceopen.com)
  • Effect of calmodulin kinase II (CaMKII) inhibition on decay of ACh and bradykinin-induced [Ca2+]i transients in human ASM cells. (brinda.info)
  • In separate experiments using human ASM homogenates, we evaluated the rate of 45Ca uptake as an index of SR Ca2+ reuptake under specific conditions. (brinda.info)
  • Error bars: s.e.m. (= 5 experiments) (c) Thapsigargin-stimulated cells were lysed and analyzed by immunoblotting with the phosphotyrosine antibodies 4G10 and RC20. (mdm-inhibitors.com)
  • 1. In this study we have investigated δ and μ opioid receptor-mediated elevation of intracellular Ca 2+ concentration ([Ca 2+ ](i)) in the human neuroblastoma cell line, SH-SY5Y. (edu.au)
  • The aim of this study was to evaluate the effects of the A 2A R agonist CGS21680 on human control and NPC1 fibroblasts. (jneurosci.org)
  • Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. (ed.ac.uk)
  • In this study, the effects of pharmacological concentrations of melatonin (1 μM-1 mM) on human pancreatic stellate cells (HPSCs) have been examined. (crcm-marseille.fr)
  • Here we describe the 3.2 Å cryo-EM structure of human DEC-205, thereby illuminating the structure of the mannose receptor protein family. (uci.edu)
  • Western analysis showed that both human pulmonary artery smooth muscle and porcine ASM displayed significant PLB protein, confirming the ability of the antibody to detect PLB from different species and tissues. (brinda.info)
  • To confirm the identity of this protein, DT40 cells or Stim1-overexpressing DT40 cells were stimulated over time with thapsigargin or CPA in the presence or absence of extracellular Ca2+, and the phospho-Erk (pErk) responses were analyzed by circulation cytometry. (mdm-inhibitors.com)
  • Thapsigargin (100 nM), an agent which discharges intracellular Ca 2+ stores, also blocked the opioid elevations of [Ca 2+ ](i). 9. (edu.au)
  • Solar panel Nov 27, 2021 · The plant-based antiviral agent thapsigargin (TG), derived from a group of poisonous plants known as 'deadly carrots', appears to be effective against all variants of SARS-CoV-2 in the lab - and that includes the quick-spreading Delta variant. (zusammen-klappt-das.de)
  • Regush, an ABC News science journalist, is on the trail of a new virus, human herpes virus-6 (HHV-6). (zusammen-klappt-das.de)
  • A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
  • In this study, we show that treatment with gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum , induced nonapoptotic, lysosome-associated cell death in human esophageal cancer cells. (oncotarget.com)
  • In this study, we found that lapatinib induced cytotoxicity in human hepatoma Huh7, HepG2 and HA22T cells. (oncotarget.com)
  • While investigating the effect of human milk on bacterial adherence to a human lung cancer cell line, we were surprised to discover that the milk killed the cells. (lu.se)
  • It is not known whether the secondary modifications to the guaianolide occur before, or after the formation of thapsigargin, but will need to be considered when elucidating the true biosynthesis. (wikipedia.org)
  • In conclusion, lapatinib induced autophagic cell death and the growth of human hepatoma cells. (oncotarget.com)
  • Pretreatment of these cells with thapsigargin caused a direct increase in I(sc) and inhibited the response to UTP. (brighton.ac.uk)
  • Our research group is interested in a broad field of chronobiology research including the examination of molecular clock functions, studying circadian control of the immune system and exploring human behavioural rhythms. (semmelweis.hu)
  • In particular, the dialogue between T cells and beta cells is far more complex in humans and recent evidence supports potential type 1 diabetes 'endotypes' based on age at onset [ 8 , 9 ]. (springer.com)
  • Taken together, this work suggested a novel therapeutic option by Gyp-L through the induction of an unconventional ROS-ER-Ca 2+ -mediated cell death in human esophageal cancer. (oncotarget.com)