Disease relevance of NSC381866

• Application of an autophagy inhibitor that works after the association of LC3 with autophagosome membrane, such as bafilomycin A1, is expected to enhance the cytotoxicity of TMZ for malignant gliomas [1].
• The transformed cells became resistant to polyamine toxicity, and the resistance was overcome by bafilomycin A1, an inhibitor of vacuolar H+-ATPase [2].
• Bafilomycin A1 (Baf), a specific inhibitor of the vacuolar-type proton pump, inhibited the entry of Semliki Forest virus and vesicular stomatitis virus into BHK-21 cells [3].
• We report here the effects of bafilomycin A1 on bone resorption in vivo [4].
• Bafilomycin A1 inhibits Helicobacter pylori-induced vacuolization of HeLa cells [5].

High impact information on NSC381866

• Perforation occurred at acidic vacuolar pH (4.9-6.7) and was reduced in frequency or prevented completely when macrophages were treated with the lysosomotropic agents ammonium chloride or bafilomycin A1 [6].
• Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced zeta chain degradation, leading to the accumulation of zeta chain in large Lamp1(+) vesicles [7].
• Env-mediated autophagy is required to trigger CD4+ T cell apoptosis since blockade of autophagy at different steps, by either drugs (3-methyladenine and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally inhibited the apoptotic process [8].
• To determine the role of the VPATPase in apoptosis of cardiac myocytes, we used a potent and specific inhibitor of the VPATPase, bafilomycin A1 [9].
• In contrast, cardiac fibroblasts treated with bafilomycin A1 showed no change in p53 protein expression or pHi and did not undergo apoptosis even after 24 h of treatment [9].

Chemical compound and disease context of NSC381866

• Specific inhibitors of vacuolar H(+)-ATPase (V-ATPase), concanamycin A and bafilomycin A1, abolish bone resorption by osteoclasts [10].
• Inhibition of adenovirus penetration with bafilomycin A1 or ammonium chloride attenuated the activation of ERK-p38 and IP-10 mRNA expression following infection, suggesting that endosomal escape was required to trigger these pathways [11].
• However, after exposure of NIH 3T3 cells to hydroxyurea (HU), a compound known to increase AAV-mediated transduction in general, virions were detected in late endosomes and lysosomes, and these cells became sensitive to Baf-mediated inhibition of transduction [12].
• Inhibitory mechanisms of H(+)-ATPase inhibitor bafilomycin A1 and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption [13].
• Vanadate and Bafilomycin A1 were shown to inhibit the ATPase activity of the reconstituted binding protein-dependent ATP-binding Cassette (ABC) transporter for maltose (MalFGK2) of Salmonella typhimurium in the micromolar range [14].

Biological context of NSC381866

• Bafilomycin A1 alone caused increased DNA laddering of genomic DNA and increased nuclear staining for fragmented DNA in neonatal cardiomyocyte apoptosis in a dose- and time-dependent manner [9].
• The acidity of the Golgi lumen dissipated rapidly upon addition of bafilomycin A1, a blocker of vacuolar-type ATPases, pHG remained constant despite acidification of the cytosol by reversal of the plasmalemmal Na+/H+ antiport [15].
• Treating cells with either U-18666A, a compound that creates an NPC-like phenotype, or with bafilomycin A1, a compound that raises late endosomal pH, has no effect on labeling of NPC1-YFP, suggesting that both drugs affect processes other than NPC1 binding to cholesterol [16].
• In isolated rabbit ciliary body preparations examined under voltage-clamped conditions, bafilomycin A1 produced a concentration-dependent decrease in short-circuit current, and topical application of bafilomycin A1 reduced intraocular pressure in rabbits, indicating an essential role of the V-ATPase in ciliary epithelial ion transport [17].
• Endosomal membrane potential was required for viral infection because cotreatment of cells with monensin partially overcame the inhibitory effect of bafilomycin A1 [18].

Anatomical context of NSC381866

• The Na(+)-independent H+ extrusion was not inhibited by bafilomycin A1 (up to 10(-7) M), although a bafilomycin A1 (10(-8) M)-sensitive H+ pump was present in membrane vesicles isolated from these osteoclasts [19].
• Intracellular acidification in cardiac myocytes was also observed after 18 h of bafilomycin A1 treatment [9].
• Bafilomycin A1 was used to analyze the association between GFP-ATP7B and the late endosomes [20].
• RESULTS: In CFPAC-1 and CHO cells, intracellular alkalization by reducing carbon dioxide concentrations in a carbon dioxide incubation chamber or intra-Golgi alkalization by bafilomycin A1 treatment increased the membrane expression of DeltaF508 protein and cystic fibrosis transmembrane conductance regulator-dependent anion transport [21].
• Although recycling of endocytosed Tf to the plasma membrane continued in the presence of Baf, recycled Tf did not dissociate from its receptor, indicating failure of Fe3+ release due to a neutral endosomal pH [22].

Associations of NSC381866 with other chemical compounds

• The time course of appearance of the adenylate cyclase activity and of bafilomycin A1 action suggests that EF enters the cytosol from late endosomes [23].
• The effect of VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i was studied by flow cytometry with propidium iodide, seminaphthorhodafluor (SNARF)-1-AM, and indo-1-AM staining, respectively [24].
• Pharmacological analysis revealed that the GRGDSP-induced Ca(2+) response was unrelated to Ca(2+) influx and the inositol triphosphate receptor-gated Ca(2+) store, but partially blocked by ryanodine or inhibition of lysosomerelated acidic organelles with bafilomycin A1 [25].
• However, only inhibition of Cat D activity by pepstatin A inhibited the early apoptotic events and delayed cell death, even in the presence of bafilomycin A1, an inhibitor of vacuolar type H+-ATPase, which inhibits acidification in lysosomes [26].
• Viral infection was totally inhibited by 30 nM Baf while endocytosis of the virus or fluorescein isothiocyanate-dextran was not affected [3].

Gene context of NSC381866

• Importantly, bafilomycin A1 reverses CAL-mediated CFTR degradation [27].
• Blocking receptor trafficking to lysosomes with bafilomycin A1 had no effect on basal turnover of either subtype but blocked agonist-stimulated beta 2AR turnover [28].
• Blocking TIMP-2 degradation with bafilomycin A1 significantly increased cell-associated TIMP-2 levels in the presence of high calcium [29].
• U1 RNA-stimulated, but not TLR-3 ligand-stimulated, IFN-I was blocked by bafilomycin A1, indicating that immunostimulation by U1 RNA requires endosomal acidification [30].
• High copy expression of STV1 partially restores vacuolar acidification in a delta vph1 mutant strain; solubilization and fractionation of membrane proteins from these vacuoles show that Stv1p co-purifies with bafilomycin A1-sensitive ATPase activity and with the 60- and 69-kDa V-ATPase subunits [31].

Analytical, diagnostic and therapeutic context of NSC381866

• Double immunofluorescence studies showed that in the presence of Baf the viral glycoproteins were found in and around mannosidase II-positive Golgi structures [3].
• Immunogold electron microscopy showed that EGF was transported into lysosomes irrespective of the addition of bafilomycin A1 [32].
• Using isolated human monocytes and ELISA, we found that colchicine (0.1 mM), cytochalasin D (30 and 300 microM), NH4Cl (30 mM), and bafilomycin A1 (1 microM) significantly reduced the effect of HBP (10 microg/ml) to enhance LPS (10 ng/ml)-induced TNF-alpha release after 24 h [33].
• Bafilomycin A1 inhibits the action of tetanus toxin in spinal cord neurons in cell culture [34].
• After treatments with cariporide or bafilomycin A1, insulin stimulation of insulin receptor and insulin receptor substrate-1 phosphorylation and Akt activity were normal [35].

References