Disease relevance of BAPTA-AM

• Activation of NF-kappaB is attenuated by pertussis toxin and inhibitors of protein kinase C, and it is completely blocked by the Ca2+ chelator BAPTA-AM [1].
• Further examinations revealed that TRPV1-induced toxicity was accompanied by increases in intracellular Ca(2+), and mitochondrial damage; these effects were inhibited by capsazepine, I-RTX, and the intracellular Ca(2+) chelator BAPTA-AM [2].
• The exit of vesicular stomatitis virus G from a pre-Golgi compartment and the exit of Shiga toxin from an endosomal compartment are sensitive to the membrane-permeant calcium chelator 1,2-bis(2-amino phenoxy)ethane-N,N,N',N'-tetraacetic acid-tetrakis (acetoxymethyl ester) (BAPTA-AM) [3].
• Hypoxia to ECs increased ERK phosphorylation within 10 min and which was abolished by administration of PD98095, calphostin C, and BAPTA/AM [4].
• 2. STDs and SWs persisted in the presence of tetrodotoxin, nifedipine and ryanodine, and upon brief exposure to Ca2+-free Cd2+-containing solutions; they were enhanced by ACh and blocked by BAPTA AM, cyclopiazonic acid and caffeine [5].

High impact information on BAPTA-AM

• Cytoprotection is abolished after treatment with cyclosporin A (CsA), which disrupts mitochondrial calcium signalling, or with the calcium chelator BAPTA-AM [6].
• However, the endothelial responses to alveolar TNF-alpha were blocked by alveolar preinjection of the intracellular Ca(2+) chelator BAPTA-AM, or the cPLA(2) blockers AACOCF(3) and MAFP [7].
• Preincubation of each of the endothelial cell lines with the calcium chelator 1,-2-bis(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acetomethyl ester (BAPTA/AM) prevented the expression of VCAM-1 and E-selectin [8].
• Although the calcium channel antagonists Zn2+ (100 microM), nifedipine (10 microM), or ruthenium red (10 microM), or the cytosolic calcium chelator BAPTA-AM (50 microM) each strongly impaired PACAP-induced secretion, transcriptional activation of chromogranin A remained unaltered [9].
• Intracellular Ca chelator BAPTA/AM and calmodulin antagonist W-7, but not Ca channel blocker nicardipine, significantly inhibited ET-3- or IRL 1620-induced cGMP generation [10].

Chemical compound and disease context of BAPTA-AM

• METHODS: To resolve the mechanism of TG induced growth arrest, rat AT3.1 prostatic cancer cells were analyzed for RNA and protein expression of the growth arrest gene, gadd153, intracellular free Ca2+ levels (Cai), and cell cycle distribution on exposure to TG alone and in combination with Ca2+ chelation induced by BAPTA-AM or BAPTA-AM/EGTA [11].
• Calcium ions play an important role in veratridine-induced chromaffin cell death because the cell permeant Ca(2+) chelator BAPTA-AM and extracellular Ca(2+) removal completely prevented veratridine-induced toxicity [12].
• Both DNA synthesis and phosphorylation of MAPK in response to SP were attenuated by pretreatment with pertussis toxin, genistein, D609, U73122, staurosporine, removal of Ca(2+) by BAPTA/AM plus EGTA, PD98059, and SB202190 [13].
• The effect of the membrane-permeant calcium chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM) on ionomycin-induced cellular calcium overload was studied in single differentiated NH15-CA2 neuroblastoma x glioma hybrid cells [14].
• Glucose deprivation and hypoxia decreased (Na(+)+K+)-ATPase activity in the absence of extracellular Ca2+, but the effects were blocked by 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-acetomethyl ester (BAPTA-AM), a chelator of intracellular Ca2+ [15].

Biological context of BAPTA-AM

• Cotreatment of growth plate chondrocytes with RA and BAPTA-AM, a cell permeable Ca2+ chelator, inhibited the up-regulation of annexin gene expression and mineralization of these cultures [16].
• This effect was largely overcome by loading cells with BAPTA-AM, highlighting the importance of mitochondrial Ca2+ buffering in shaping the release kinetics [17].
• An interesting finding was that acute treatment of cells with BAPTA-AM activated capacitative Ca2+ entry at the plasma membrane, due to its efficient hydrolysis in the stores, and the ensuing decrease in the endoplasmic reticulum [Ca2+] [18].
• Buffering the Ca(2+) increase with the cytoplasmic Ca(2+) chelator BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N1,N-tetraacetic acid] blocks RC3-induced apoptosis, indicating that the rise in intracellular Ca(2+) is required for apoptotic death [19].
• This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation [20].

Anatomical context of BAPTA-AM

• Furthermore, we show that L1- and K+(-)dependent neurite outgrowth can be specifically inhibited by a reduction in extracellular calcium to 0.25 microM, and by pretreatment of cerebellar neurons with the intracellular calcium chelator BAPTA/AM [21].
• Additionally, the response could be fully inhibited by preloading PC12 cells with BAPTA/AM which buffers changes in intracellular calcium [22].
• Both responses were significantly reduced by pre-treatment with sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) pump inhibitors or with the intracellular Ca(2+) chelator BAPTA-AM [23].
• Pretreatment of myocytes with the intracellular Ca2+ chelator BAPTA-AM prevented the ATP-stimulated increase in cytosolic Ca2+ and attenuated the ATP-stimulated increase in c-fos expression [24].
• Omission of Ca2+ from the incubation medium or loading synaptosomes with the Ca2+ chelator BAPTA-AM (20 and 100 mumol/L) prevented NE release, indicating a Ca(2+)-dependent mechanism [25].

Associations of BAPTA-AM with other chemical compounds

• Moreover, shear stress-induced ET-1 gene expression was inhibited by EGTA, BAPTA/AM, and staurosporine to a degree similar to the inhibition of actin depolymerization [26].
• Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability [20].
• Although downregulation of PKC did not suppress Ang II-induced activation of MAP kinase and RSK, chelating intracellular Ca2+ by BAPTA-AM completely abolished Ang II-induced activation of these kinases [27].
• We measured the effect of insulin on (1) secretin-stimulated cAMP levels in cholangiocytes and duct expansion in intrahepatic bile duct units (IBDUs) in the absence or presence of BAPTA/AM, H7 or rottlerin and (2) bile flow [28].
• VP-induced alterations were also prevented by pretreatment with the Ca2+-buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase II antagonist, calmidazolium [29].

Gene context of BAPTA-AM

• Akt activation is abolished by the phospholipase C-gamma inhibitor U-73122, by the intracellular calcium chelator BAPTA-AM, and by the specific calmodulin antagonist W-7 [30].
• GnRH-induced JNK activity was reduced after treatment with the intracellular calcium chelator BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester), whereas activation of ERK was not affected [31].
• Moreover, the effect of this compound on CYP1A1 was strongly abolished in the presence of BAPTA-AM, a well known chelator of intracellular calcium, and 2-aminoethyl diphenylborate, an inhibitor of store-operated calcium channels [32].
• An increase in intracellular calcium with the calcium ionophore A23187 or intracellular calcium chelation by BAPTA-AM had no effect on either basal or FXa-induced VEGF secretion, suggesting that the calcium signaling pathway was not sufficient to induce VEGF secretion [33].
• Intracellular Ca(2+) chelator BAPTA/AM or cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor H-89 partially blocked the inhibitory effects of PGE(2) on CCL27 production and NF-kappaB activity, and the addition of both completely abrogated the inhibition [34].

Analytical, diagnostic and therapeutic context of BAPTA-AM

• 3. The influence of cytoplasmic Ca2+ ligands was characterized by internal perfusion with high concentrations of diffusible Ca2+ ligands (indo-1) or by superfusion with the membrane-permeant Ca2+ ligand, BAPTA AM [35].
• Preincubation of cells in BAPTA-AM ester was also protective, indicating that the injury was triggered by Ca(2+) influx during reperfusion [36].
• Cortical cell cultures exposed to 20 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, underwent neuronal apoptosis within 12 h that was evident by shriveled cell bodies, aggregated and condensed nuclear chromatin, and disrupted nuclear membrane [37].
• First, by determining the spatial distribution of BAPTA through immunocytochemistry and confocal microscopy of cortical neurons loaded with BAPTA/AM and, second, by determination of the kinetics of loading and efflux of BAPTA through enzyme-linked cell immunoassays (ELISA) and immunocytochemistry [38].
• Denaturing Western blots of extracts from lymphocytes incubated with 2-chlorodeoxyadenosine, aphidicolin and/or BAPTA-AM clearly demonstrated that dCK protein levels were unchanged during these treatments [39].

References