EndoplasmicInhibitorSERCACalcium ATPaseDepletionApoptosisPumpAcidicProdrugActivityEffectsTargetSimilarFormationCellsEndoplasmic reticulumInhibitor thapsigarginSARCOPLASMIC RETICULUMInhibitorsIntracellularPMCAInhibitsHomeostasisMammalianIncreasing cytosolicHistamineSynthesisConcentration-dependentMembraneDysfunctionResistanceSignificantlyOccurResultsSpecificCommonReleaseComplete
Endoplasmic13
- Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
- Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. (wikipedia.org)
- Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. (kcl.ac.uk)
- 2. Thapsigargin, a specific inhibitor of Ca 2+ -ATPase on the endoplasmic reticulum, and ryanodine and ruthenium red, inhibitors of the ryanodine receptor, blocked the induction of LTD. 3. (elsevierpure.com)
- In intact arterial segments pre-stimulated with 20 mM K(+), 5-HT-evoked contractions were unaffected by 1 microM thapsigargin, which inhibits sarco- and endoplasmic reticulum calcium-ATPases. (ox.ac.uk)
- 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)
- Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. (hal.science)
- It was initially described as a tumor promoting agent that induces rapid Ca 2+ release from intracellular stores 3 by the inhibition of the sarcoplasmic endoplasmic reticulm Ca 2+ -dependent ATPase pump without inositol phosphate formation 4 . (alomone.com)
- uPA attenuated MonoMac6 (MM6) macrophage-like cell line apoptosis induced by oxidized LDL (Ox-LDL) and by thapsigargin (inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPase), but not by staurosporine (protein kinase inhibitor), suggesting that uPA antiapoptotic activity is Ca(2+)-independent, but involves a kinase activation. (monocyte.eu)
- 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)
- 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)
- In the first instance, a dominant mutant for the sarco-endoplasmic reticular Ca 2+ -ATPase (SERCA) pump was introduced into itpr mutant backgrounds. (jneurosci.org)
- Computational studies were enrolled to predict the interaction of the synthesized compound with sarco-endoplasmic reticulum (SR) Ca 2+ transport ATPase (SERCA), a target of relevance for developing new therapeutics against arthritis. (mdpi.com)
Inhibitor4
- 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)
- Meanwhile, research aimed to deci- laria parasites was initially based on the structural resemblance of pher the underlying mechanisms of ART resistance has become a ARTs to thapsigargin, a specific inhibitor of mammalian SERCAs. (2medicalcare.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)
SERCA3
- Since inhibition of SERCA is a mechanism of action that has been used to target solid tumors, thapsigargin has attracted research interest. (wikipedia.org)
- The removal of Ca 2+ from the cytosol, which terminates the contraction, can be either via the Na + -Ca 2+ exchanger, which reversibly exchanges Ca 2+ ions for Na + ions across the cell membrane or by Ca 2+ re-uptake to the SR and the mitochondria (by the PAMCA and the SERCA ATPase pumps) 1,3 . (alomone.com)
- Since PfATP6 is the only SERCA-type Ca2⫹-ATPase in the malaria ARTs contain an endoperoxide bridge that is essential for the parasite's genome, it was evaluated as the target of ARTs. (2medicalcare.com)
Calcium ATPase1
- It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM. (bvsalud.org)
Depletion3
- 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)
- Thapsigargin-induced depletion of Ca 2+ stores causes apoptosis in most cell lines 5 . (alomone.com)
Apoptosis2
- 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)
Pump2
- The CV-system is also assumed to be involved in Ca 2+ -transport since it contains a PMCA-type Ca 2+ -ATPase (PAT1), calmodulin [ 3 ] and a vacuolar proton pump that establishes a proton gradient for Ca 2+ -transport [ 4 ]. (biomedcentral.com)
- One possibility is that sphingolipids could lessen the activity of vacuolar ATPase, the proton pump in lysosomes that maintains their acidic internal environment. (alzforum.org)
Acidic1
- Acidic means that the stores are equipped with a V-type H + -ATPase. (biomedcentral.com)
Prodrug1
- A prodrug of thapsigargin, mipsagargin, is currently undergoing clinical trials for the treatment of glioblastoma. (wikipedia.org)
Activity4
- The biological activity has also attracted research into the laboratory synthesis of thapsigargin. (wikipedia.org)
- 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)
- Thapsigargin Epoxide is a non-active analogue of Thapsigargin and can be used as a negative control for Thapsigargin activity 9,10 . (alomone.com)
- TG is usually a well-characterized ER stress-inducing agent23 that induces ER stress in the cell by binding Cangrelor biological activity to and inhibiting Ca2+-ATPase, an ER resident transmembrane protein that maintains Ca2+ homeostasis24. (ampkpathway.com)
Effects1
- Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. (ed.ac.uk)
Target1
- ATPase PfATP6 has been postulated as a specific target of ARTs. (2medicalcare.com)
Similar1
- In contrast to Orai1 abundance, the Na + /K + ATPase protein abundance was similar without mAR activation (24.5 ± 1.1 a.u., n = 5) and 1 h (24.7 ± 2.2 a.u., n = 5) or 2 h (25.0 ± 1.9 a.u., n = 5) following mAR activation. (biomedcentral.com)
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)
Cells2
- Thapsigargin and tunicamycin each significantly activated caspase-3, -9, and -2 in the intrinsic apoptotic pathway in SH-SY5Y cells. (elsevierpure.com)
- Thapsigargin and tunicamycin decreased the mitochondrial membrane potential in SH-SY5Y cells. (elsevierpure.com)
Endoplasmic reticulum14
- Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). (wikipedia.org)
- The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) plays a critical role in Ca2+ homeostasis via sequestration of this ion into the sarco/endoplasmic reticulum. (ku.edu)
- A comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. (nih.gov)
- Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. (unl.pt)
- Thapsigargin (TG) is a potent inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases (SERCAs). (nih.gov)
- P 2 - type calcium ATPases ( ACA s-auto inhibited calcium ATPases and ECA s-endoplasmic reticulum calcium ATPases) belong to the P- type ATPase family of active membrane transporters and are significantly involved in maintaining accurate levels of Ca 2+ , Mn 2+ and Zn 2+ in the cytosol as well as playing a very important role in stress signaling, stomatal opening and closing and pollen tube growth. (biomedcentral.com)
- P 2A - type ATPases form a distinct set of ER-type Ca 2+ ATPases, generally called ECA s and are closely related to the animal sarco-endoplasmic reticulum Ca 2+ pump SERCA1 [ 9 ]. (biomedcentral.com)
- Cellular Ca2+ was increased by the use of the endoplasmic reticulum Ca2+ ATPase inhibitor, thapsigargin. (ku.dk)
- In intact arterial segments pre-stimulated with 20 mM K(+), 5-HT-evoked contractions were unaffected by 1 microM thapsigargin, which inhibits sarco- and endoplasmic reticulum calcium-ATPases. (ox.ac.uk)
- Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. (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)
- the endoplasmic reticulum Ca2+ discharge with Ca2+-ATPase inhibitors cyclopiazonic acidity (5 M) or thapsigargin (5 M) almost abolished ( 20 % control) the upsurge in [Ca2+]i and power response to CS. (conferencedequebec.org)
- In CEPT1-deficient muscles, an altered SR phospholipid milieu decreased sarco/endoplasmic reticulum Ca 2+ ATPase-dependent calcium uptake, activating calcium-signaling pathways known to improve insulin sensitivity. (diabetesjournals.org)
- Indeed, RNA disturbance promotes the apoptosis of murine embryonic fibroblasts treated with tunicamycin or thapsigargin, two inducers of endoplasmic reticulum tension5. (synanet2020.com)
Inhibitor thapsigargin2
- this was also inhibited by the SERCA inhibitor thapsigargin. (ku.edu)
- Intravesicular 45 Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca 2+ -ATPase inhibitor thapsigargin. (johnshopkins.edu)
SARCOPLASMIC RETICULUM3
- It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM . (bvsalud.org)
- In silico study was carried out to examine the interaction between lupene-ol and lupene-on on Sarcoplasmic Reticulum Ca 2 +-ATPase. (ijtpr.com)
- Both of the compounds blockade the sarcoplasmic reticulum Ca 2+ -ATPase and inhibite the Ca 2+ uptake from intracellular cytosolic. (ijtpr.com)
Inhibitors2
- Thapsigargin, but not inhibitors of plasma membrane or mitochondrial Ca2+ pumps/channels, completely attenuated the increase in intracellular Ca2+ consistent with a critical role for SERCA in maintaining endothelial cell Ca2+ homeostasis. (ku.edu)
- This ATP-dependent activity was stimulated by Ca2+ and Mg2+ ions and by calmodulin, and was inhibited by pump inhibitors (sodium orthovanadate or thapsigargin). (hal.science)
Intracellular3
- 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 (TG), 2,5-t-butylhydroquinone (tBHQ) and cyclopiazonic acid (CPA) all inhibit the initial Ca(2+)-response to thyrotropin-releasing hormone (TRH) by depleting intracellular Ca2+ pools sensitive to inositol 1,4,5-trisphosphate (IP3). (nih.gov)
- Previous studies on pulmonary arterial smooth muscle cells have shown that nicotinic acid adenine dinucleotide phosphate (NAADP) evokes highly localized intracellular Ca(2+) signals by mobilizing thapsigargin-insensitive stores. (ox.ac.uk)
PMCA3
- The P 2B - type ATPases are characterized by the binding of calmodulin to their auto inhibitory terminal domains and show similarities to animal CaM-stimulated Ca 2+ ATPases (PMCA). (biomedcentral.com)
- An increase in expression level of plasma membrane calcium ATPase (PMCA) isoforms 1 and 4 occur during a late phase of osteoclast differentiation [ 13 , 14 ]. (biomedcentral.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)
Inhibits1
- Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. (wikipedia.org)
Homeostasis2
- The data indicated that expression of ECA s is enhanced under calcium stress, suggesting possible roles of these ATPases in calcium homeostasis in wheat. (biomedcentral.com)
- However, less expression of these isoforms results in low bone mass in mice which indicated a clear role of PMCAs in the proper development of osteoclast and bone homeostasis [ 15 ] These ATPases also have significant importance in plants. (biomedcentral.com)
Mammalian1
- Meanwhile, research aimed to deci- laria parasites was initially based on the structural resemblance of pher the underlying mechanisms of ART resistance has become a ARTs to thapsigargin, a specific inhibitor of mammalian SERCAs. (chestervetclinic.com)
Increasing cytosolic1
- Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion. (wikipedia.org)
Histamine2
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)
Concentration-dependent1
- The Na + , K + -ATPase inhibitor ouabain induced concentration-dependent neuronal death. (jneurosci.org)
Membrane1
- We have looked for a Ca2+-transport ATPase in tachyzoites and found Ca2+-ATPase activity (11-22 nmol Pi liberated/mg protein/min) in the tachyzoite membrane fraction. (hal.science)
Dysfunction1
- Energy deficiency and dysfunction of the Na + , K + -ATPase are common consequences of many pathological insults. (jneurosci.org)
Resistance1
- Thapsigargin resistance in human prostate cancer cells. (nih.gov)
Significantly1
- 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)
Occur1
- 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)
Results1
- Our results demonstrate that serosal addition of thapsigargin causes a release of prostaglandin E2 from the dermis below the transporting epithelium. (ku.dk)
Specific1
- ATPase PfATP6 has been postulated as a specific target of ARTs. (chestervetclinic.com)
Common1
- This pattern highlights the common ancestry of P 2− type calcium ATPases. (biomedcentral.com)
Release1
- 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)
Complete1
- The complete biosynthesis of thapsigargin has yet to be elucidated. (wikipedia.org)