Endoplasmic reticulumInhibitorConcentrationIntracellularSERCADepletionInducerIRE1HistamineMONOCYTESInhibitorsSubcellularProteinExtracellularFreePresenceSuggestStressResultsResponseEffectsActivityTreatmentEndoplasmicFree cytosolicSynthesisApoptosisTumorsMicroMCalmodulinEndothelialDependenceIncreasesSignificantlyCellsStudyCellReleaseFormationRole
Endoplasmic reticulum7
- Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
- 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)
- SERCA is responsible for pumping cytosolic Ca 2+ into the endoplasmic reticulum (ER) store and thus maintaining the intracellular concentrations of Ca 2+ both in the cytosol and in the ER store. (jneurosci.org)
- 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)
- Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. (hal.science)
- Calcium spikes were inhibited by thapsigargin (Tg), indicating that they originated from endoplasmic reticulum. (superdocdc.com)
- Moreover the effects of high glucose on caspase 3 activation and lamin B degradation were mimicked by thapsigargin a known inducer of endoplasmic reticulum stress [ER stress]. (buyresearchchemicalss.net)
Inhibitor3
- the ER stress-inducing agent thapsigargin an inhibitor from the sarco(endo)plasmic reticulum Ca2+ pump that triggers Ca2+ efflux from ER shops elevated cytosolic [Ca2+] and induced TF PCA. (healthcarecoremeasures.com)
- Conversely, using nuclear-cytosolic fractionation on ER stressed cells, we found that these pre-miRNAs were decreased in the nuclear fractions without the IRE1 inhibitor. (biomedcentral.com)
- On the other hand, further research proved that downregulating TRPC3 by siRNA or applying with Pyrazole-3 (Pyr3), a extremely selective inhibitor of TRPC3, reduced DAG-, thapsigargin- and Ang IIinduced Ca2+ influx in monocytes from SHR (Liu et al. (flapinhibitor.com)
Concentration4
- Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
- The Ca 2+ signal is characterized by a rapid increase in the concentration of free cytosolic calcium ([Ca 2+ ] i ) attributable to the opening of calcium channels located in the plasma membrane and in the membranes of intracellular calcium stores. (jneurosci.org)
- 0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. (ed.ac.uk)
- We investigated phagocytosis and intracellular killing of an attenuated strain of Mycobacterium tuberculosis (H37Ra) by human neutrophils focusing on the role of the cytosolic free calcium concentration [Ca2+]I and certain cytosolic calcium-dependent membrane-binding proteins annexins. (superdocdc.com)
Intracellular1
- Critical evaluation of the role of calcium as an intracellular messenger requires measurement of cytosolic free calcium concentrations, and comparison with varied stimuli and cell responses. (essay9.com)
SERCA1
- Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
Depletion2
- 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)
Inducer1
- HepG2 cells were stimulated with an ER stress inducer thapsigargin (TG) for 24 h to mimic ER stress in vitro. (utmb.edu)
IRE12
- The cytosolic part of IRE1 provides the kinase and endoribonuclease (RNase) domains. (ampkpathway.com)
- IRE1 (ERN1) is a protein kinase and endoribonuclease that facilitates cytosolic splicing of (XBP1s) mRNA, thereby Benzylpenicillin potassium enhancing expression of the XBP1s isoform, which induces transcription of genes involved in Benzylpenicillin potassium ER-associated protein degradation (ERAD), lipid synthesis, and protein folding (7, 8). (iwap2018.com)
Histamine1
- Both blockers also reduced histamine-induced cytosolic Ca(2+) elevation. (unige.ch)
MONOCYTES1
- 2009). In monocytes, DAG-, thapsigargin- and Ang II-induced Ca2+ influxes have been elevated in response to pathological state in SHR. (flapinhibitor.com)
Inhibitors1
- 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)
Subcellular1
- Individual subcellular fractions namely the cytosolic fraction [fraction F1] membrane/organelle protein. (buyresearchchemicalss.net)
Protein2
- Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. (hal.science)
- In response to ER stress, ATF6 transits from the ER to the Golgi apparatus, where it is cleaved, releasing an N-terminal cytosolic fragment (ATF6-N) that enters the nucleus and activates UPR target genes involved in protein folding and transport (6, 9). (iwap2018.com)
Extracellular1
- These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. (ed.ac.uk)
Free2
- Free Ca 2+ is then rapidly sequestered by the action of calcium pumps and exchangers and also with buffering by cytosolic calcium binding proteins. (jneurosci.org)
- Using single-cell ratio imaging of Fura-2-loaded neutrophils, we demonstrate that the heterogeneity and asynchrony of the oxidase response originates from variability in the timing and magnitude of the cytosolic free Ca2+ signal. (superdocdc.com)
Presence2
- Analysis of leak in the presence of 25μM thapsigargin and 6muM ruthenium red indicates a simple linear relationship between [Ca2+]SR and the rate of Ca2+ leak. (gla.ac.uk)
- D) WT or alleles were cultured in the presence or absence of 1 M thapsigargin for 6 h, and mRNA levels were measured by RT-qPCR. (iwap2018.com)
Suggest1
- This can lead to accumulation of cytosolic PrP, especially under ER stress conditions, and to alternative membrane orientation.7,10 The existence of many conformers, glycoforms and topological variants may suggest that PrP exploit posttranslational modifications to increase its diversity. (fabretp.org)
Stress1
- TRPC6 is actually a ubiquitous TRPC isoform expressed in the whole vasculature, which plays a pivotal function in blood stress regulation because of its physiological value in both receptor-mediated and pressure-induced increases of cytosolic Ca2+ in VSMCs (Toth et al. (flapinhibitor.com)
Results1
- In keeping with these results anti-GRP78 autoantibodies which were isolated in the serum of sufferers with prostate cancers and bind to a particular N-terminal epitope (Leu98-Leu115) on cell surface area GRP78 triggered a dose-dependent upsurge in cytosolic [Ca2+] and improved TF PCA. (healthcarecoremeasures.com)
Response1
- Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. (ed.ac.uk)
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)
Activity2
- The biological activity has also attracted research into the laboratory synthesis of thapsigargin. (wikipedia.org)
- Cell proliferation, migration and cell death are regulated by alterations of cytosolic Ca 2+ activity [ 20 - 23 ]. (biomedcentral.com)
Treatment1
- A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
Endoplasmic6
- Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
- Here, we report that when [Ca(2+)](i) handling was disrupted by blocking Ca(2+) uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1-5 microM) or insulin (200 nM), K(slow) was transiently potentiated and then inhibited. (nih.gov)
- PCB 95 did not significantly alter levels of resting cytosolic Ca2+ nor thapsigargin-sensitive Ca2+ stores, suggesting a more complex mechanism than sensitization from increased cytosolic Ca2+ or an increased endoplasmic reticulum/cytosolic Ca2+ gradient. (nih.gov)
- Compounds used for the study included modulators of the extracellular Ca2+ concentration (CaCl2, EGTA), a calcium ionophore (ionomycin), membrane permeant Ca2+ chelators (BAPTA-AM, EGTA-AM) and an endoplasmic reticulum Ca2+-ATPase inhibitor (thapsigargin). (lavoixdesrroms.org)
- Vemurafenib-treated melanoma cells showed increased cytosolic concentration of calcium, a potential trigger for endoplasmic reticulum (ER) stress, which can lead to apoptosis. (crcm-marseille.fr)
- Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. (hal.science)
Free cytosolic1
- 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)
Synthesis2
- The biological activity has also attracted research into the laboratory synthesis of thapsigargin. (wikipedia.org)
- Incubation with thapsigargin resulted in decreased EPO synthesis ( 0.05) but stimulated VEGF secretion ( 0.05). (lavoixdesrroms.org)
Apoptosis2
- In the present study, we examined whether dexmedetomidine exerts inhibitory effects on apoptosis mediated by thapsigargin-induced ER-stress in SH-SY5Y cells, and proposed a possible underlying mechanism for its neuroprotective effects. (aimspress.com)
- In melanoma cells with low sensitivity or resistance to vemurafenib, combination treatment with thapsigargin augmented or induced apoptosis. (crcm-marseille.fr)
Tumors1
- Moreover, the ER stress inducer thapsigargin prevented invasive growth of tumors formed from vemurafenib-sensitive melanoma cells in vivo. (crcm-marseille.fr)
MicroM1
- Thapsigargin increased global cytosolic Ca2+ and activated a I(SOC), which was small (-35 pA @ -80 mV), reversed near +40 mV, inhibited by 50 microM La3+, and exhibited anomalous mole fraction dependence. (nih.gov)
Calmodulin1
- Thapsigargin-evoked Ca 2+ or calmodulin little affected rsTRPA1 activity or thermosensitivity, implying the importance of precise spatiotemporal action of Ca 2+ . (molcells.org)
Endothelial2
- 24. Thapsigargin activates Ca²+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells. (nih.gov)
- The basal cytosolic pH (pH(i)) of endothelial monolayers in a 5% CO 2 -HCO 3 / - buffer was 7.27 ± 0.02 and that in a bicarbonate-free solution was 7.22 ± 0.03. (johnshopkins.edu)
Dependence1
- Remarkably, a single rattlesnake-mimicking substitution in the conserved but presumably dormant cytosolic Ca 2+ -binding domain of bTRPA1 substantially enhanced thermosensitivity through cytosolic Ca 2+ like rsTRPA1, indicating the capability of this single site in the determination of both cytosolic Ca 2+ dependence and thermosensitivity. (molcells.org)
Increases1
- Co-incubation with dexmedetomidine suppressed thapsigargin-induced increases in cytosolic Ca 2+ , caspase-4 and -3 activity, eIF2α phosphorylation, and expression of ER-stress biomarkers. (aimspress.com)
Significantly1
- In the presence of atipamezole or efaroxan, but not BU99006, inhibition of eIF2α phosphorylation and CHOP expression significantly increased following treatment with dexmedetomidine in thapsigargin-treated cells. (aimspress.com)
Cells3
- We used thapsigargin (TG) to generate an ER-stress response in SH-SY5Y cells. (aimspress.com)
- Plasma membrane Ca2+-ATPase (PMCA) has a vital part in maintaining cytosolic calcium mineral focus ([Ca2+]via PMCA inhibition in major dermal fibroblasts and MDA-MB-231 breasts tumor cells. (buyresearchchemicalss.net)
- We propose that metabotropic receptor-mediated TRP channel activation can contribute to cytosolic calcium signaling in Müller cells. (arvojournals.org)
Study1
- Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. (hal.science)
Cell1
Release1
- Buffering of cytosolic Ca(2+) by exposure of myocytes to BAPTA-AM (5 μm) reduced I(CaL) amplitude, as did inhibition of Ca(2+) release from the sarcoplasmic reticulum with ryanodine (2 μm) and thapsigargin (1 μm). (ox.ac.uk)
Formation1
- 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)
Role1
- 23. Dominant role of Orai1 with STIM1 on the cytosolic entry and cytotoxicity of lead ions. (nih.gov)