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Protein synthesisEndoplasmic reticulumInhibitorNitricInducerTumorsCalciumVitroCellsDateEffectsResearchTreatmentCriticalProteinProdrugMipsagarginInducesEndoplasmicCyclopiazonic acidityEIF2SecretoryBiosynthesisSensitivityHistamineApoptosisInhibitorsProteinsIncreasing cytosolicDepletionSignificantlyReleaseResultsStudiesTransportFreeDrug
Protein synthesis8
  • The effect of dexamethasone on mRNA and protein synthesis of lipocortins (LCT) 1, 2 and 5 has been investigated in U-937 cells. (shengsci.com)
  • The UPR activation involves three major downstream effects including reduction in protein synthesis to reduce ER load, enhancement of ER protein folding capacity and upregulation of ER-associated protein degradation (ERAD). (distantreader.org)
  • In the pancreatic acinar cell CN plays a role in mediating the action of elevated Ca 2+ to stimulate cell division, pancreatic growth and protein synthesis. (pancreapedia.org)
  • The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. (scienceopen.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)
  • These results indicate that in infected cells, gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite the presence of activated PKR. (scienceopen.com)
  • The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date. (scienceopen.com)
  • Interestingly, there existed a reciprocal positive-regulatory loop between Ca 2+ release and ER stress in response to Gyp-L. In addition, protein synthesis was critical for Gyp-L-mediated ER stress and cell death. (oncotarget.com)
Endoplasmic reticulum2
Inhibitor2
  • Knockdown of PERK by siRNA or the PERK inhibitor glycogen synthesis kinase reduced expressions of the differentiation markers, α-SMA and Col IV, in WI-38 cells. (tmu.edu.tw)
  • Conversely, either NO or cGMP analogs paired with one-train tetanization produced late-phase potentiation, and the cGMP-induced potentiation was blocked by inhibitors of protein or RNA synthesis and an inhibitor of PKG, but not by an inhibitor of PKA. (jneurosci.org)
Nitric1
Inducer1
  • Thapsigargin (TG), an ER stress inducer, elevated expressions of PERK and ER stress-related proteins with increased differentiation of WI-38 cells. (tmu.edu.tw)
Tumors1
  • Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
Calcium5
  • Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
  • 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)
  • These triggers include but are not limited to nutrient deprivation, hypoxia and disruption by chemical inhibitors of polypeptide N-linked glycosylation (e.g. tunicamycin) or calcium flux (e.g. thapsigargin), oxidative stress and infection. (distantreader.org)
  • κ-Opioid receptor expression was assessed immunocytochemically (using KA8 and KOR1 antibodies), as well as functionally by examining the effect of κ-receptor activation on intracellular calcium ([Ca 2+ ](i)) homeostasis and DNA synthesis. (uky.edu)
Vitro1
Cells1
Date1
  • To date, three distinct syntheses have been reported: one by Steven V. Ley, one by Phil Baran. (wikipedia.org)
Effects1
  • 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)
Research2
  • The biological activity has also attracted research into the laboratory synthesis of thapsigargin. (wikipedia.org)
  • PURPOSE: The objective of this synthesis research was to explore representations of autism and human-animal interactions (HAI) in the health sciences literature and the implications for autistic children and their families. (bvsalud.org)
Treatment1
  • A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
Critical1
  • METHODS: Guided by critical interpretive synthesis methods proposed by Dixon-Woods et al. (bvsalud.org)
Protein10
  • 3. Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells. (nih.gov)
  • Accompanying this general protein synthesis control, eIF2 phosphorylation induces translation of specific mRNAs, such as that encoding the bZIP (basic leucine zipper) transcriptional regulator ATF4 (activating transcription factor 4). (scienceopen.com)
  • Emetine treatment led to a decrease in viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. (bvsalud.org)
  • During many viral infections, as well as in other cellular stress conditions, changes in the phosphorylation state of eIF2, which lower the levels of the ternary complex eIF2-GTP-tRNA-Meti, result in overall inhibition of protein synthesis. (allindianpatents.com)
  • Phosphorylation of eIF2 downregulates global protein synthesis and induces gene specific translation during the ISR. (nih.gov)
  • Polysome analysis shows reduction in global protein synthesis and shift of ATF4 mRNA translation to larger polysomes in eIF2γ-I465Sfs*4 (fs) iPSCs. (nih.gov)
  • Dig2, a murine Scylla/Charybdis homolog, is also a stress-responsive protein induced by a variety of treatments including dexamethasone, thapsigargin, tunicamycin, and heat shock (Wang, 2003). (sdbonline.org)
  • Hypothalamic GnRH is the primary regulator of reproduction in vertebrates, acting via the G protein-coupled GnRH receptor (GnRHR) in pituitary gonadotrophs to control synthesis and release of gonadotropins. (nih.gov)
  • In an urgent need for new drug targets the endoplasmic reticulum (ER) has become a promising candidate since rapidly growing tumor cells upregulate their protein synthesis and therefore depend on efficient folding of nascent secretory proteins in the ER. (oncotarget.com)
  • Aim of the UPR is to re-establish ER homeostasis through reduction of protein synthesis and simultaneous overexpression of ER chaperones [ 4 ]. (oncotarget.com)
Prodrug6
  • Solid-phase synthesis protocols were developed for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavable by human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavable by prostate-specific membrane antigen. (ku.dk)
  • A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
  • 1. Mipsagargin: The Beginning-Not the End-of Thapsigargin Prodrug-Based Cancer Therapeutics. (nih.gov)
  • 4. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours. (nih.gov)
  • 11. Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug. (nih.gov)
  • 12. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. (nih.gov)
Mipsagargin1
Induces2
  • 2. Thapsigargin induces a calmodulin/calcineurin-dependent apoptotic cascade responsible for the death of prostatic cancer cells. (nih.gov)
  • Lipid overload induces insulin resistance in muscle and alters the composition of the sarcoplasmic reticulum (SR). To test the hypothesis that skeletal muscle phospholipid metabolism regulates systemic glucose metabolism, we perturbed choline/ethanolamine phosphotransferase 1 (CEPT1), the terminal enzyme in the Kennedy pathway of phospholipid synthesis. (diabetesjournals.org)
Endoplasmic7
Cyclopiazonic acidity1
EIF21
  • Western analysis shows that expression of ATF4, CHOP, and GADD34 is hyperinduced during ER stress (thapsigargin, TG) in eIF2γ-I465Sfs*4 iPSCs. (nih.gov)
Secretory1
  • T he synthesis, segregation, intracellular transport, and exocytic export of secretory proteins in eukaryotic cells is now well understood. (rupress.org)
Biosynthesis2
  • The complete biosynthesis of thapsigargin has yet to be elucidated. (wikipedia.org)
  • 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)
Sensitivity2
Histamine2
Apoptosis1
Inhibitors1
Proteins1
  • Synthesis begins on free cytosolic ribosomes that subsequently attach to the ER, resulting in the cotranslational discharge of the nascent proteins into the ER lumen. (rupress.org)
Increasing cytosolic1
  • Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion. (wikipedia.org)
Depletion2
  • Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. (wikipedia.org)
  • The increase in [Ca 2+ ](i) induced by changing from a 5 to a 20% CO 2 -HCO 3 / - solution was not significantly altered by removal of buffer Ca 2+ either before or after depletion of bradykinin- and thapsigargin-sensitive intracellular Ca 2+ stores. (johnshopkins.edu)
Significantly3
  • This treatment significantly stimulated VEGF synthesis but also decreased EPO secretion ( 0.05). (lavoixdesrroms.org)
  • Addition of prostaglandin E2 increased the cAMP contents of the isolated epithelia significantly, whereas thapsigargin had no significant effect on the cAMP level. (ku.dk)
  • The epithelium itself does not contribute significantly to the prostaglandin E2 synthesis. (ku.dk)
Release4
  • Addition of thapsigargin to isolated epithelia inhibited the Na+ transport and had no effect on the prostaglandin E2 release, though the prostaglandin E2 release from the isolated epithelia could be increased by the addition of arachidonic acid. (ku.dk)
  • Our results demonstrate that serosal addition of thapsigargin causes a release of prostaglandin E2 from the dermis below the transporting epithelium. (ku.dk)
  • Because synthesis and release of endothelium-derived vasodilatory substances are linked to an increase in cytosolic calcium concentration ([Ca 2+ ](i)), we examined the effect of intracellular acidification on cultured rat aortic endothelial cells loaded either with the pH-sensitive probe carboxy-seminaphthorhodafluor-1 or the Ca 2+ -sensitive fluorescent probe indo 1. (johnshopkins.edu)
  • This Ca 2+ mobilization may be linked to endothelial synthesis and release of vasodilatory substances during acidosis. (johnshopkins.edu)
Results1
  • The results suggest that manipulation of the Ca2+ flux and the intracellular concentration of free Ca2+ have little influence on VEGF and EPO synthesis. (lavoixdesrroms.org)
Studies1
  • 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)
Transport2
  • Serosal addition of thapsigargin to the whole frog skin increased the Na+ transport by increasing the apical Na+ permeability. (ku.dk)
  • This indicated that the response in Na+ transport was due to a Ca2+ dependent activation of the prostaglandin E2 synthesis. (ku.dk)
Free1
  • 7. Bis-(o-aminophenoxy)-ethane-N,N,N,N, tetraacetic acidity aminoethoxy (50 microM) or perfusion with nominally Ca(2+)-free of charge medium removed facilitation from the NMDA depolarization induced by 30 microM 5-hydroxytryptamine and 100 nM thapsigargin. (crispr-reagents.com)
Drug1
  • 7. Thapsigargin-From Traditional Medicine to Anticancer Drug. (nih.gov)