The Experts below are selected from a list of 7317 Experts worldwide ranked by ideXlab platform
Hiroshi Ochiai - One of the best experts on this subject based on the ideXlab platform.
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effect of Bafilomycin A1 on the growth of japanese encephalitis virus in vero cells
Journal of NeuroVirology, 1998Co-Authors: Tsugunobu Andoh, Hiroshi Kawamata, Miho Umatake, Katsutoshi Terasawa, Tsutomu Takegami, Hiroshi OchiaiAbstract:We studied the effect of Bafilomycin A1 (Baf-A1), a novel and highly specific inhibitor for vacuolar-type proton (V-H + ) pump, on the growth of Japanese Encephalitis virus (JEV) in Vero cells. Viral fluorescence microscopic study showed that Baf-A1 induced the complete disappearance of acidified compartments such as endosomes and lysosomes in Vero cells by the treatment with 0.1 mM Baf-A1 for 1 h at 378C. In proportion to the disappearance of acidified compartments, virus growth was inhibited when Baf-A1 was present from 1 h before infection to the end of incubation in a dose-dependent manner, or added within as early as 5 min after infection. Conversely, the virus growth was recovered in correlation with the reappearance of acidified compartments after removal of Baf-A1. These results suggest that a low pH condition, which is regulated by Baf-A1-sensitive V-H + pumps, is essential for the early stage of JEV growth.
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inhibitory effect of Bafilomycin A1 a specific inhibitor of vacuolar type proton pump on the growth of influenza a and b viruses in mdck cells
Antiviral Research, 1995Co-Authors: Hiroshi Ochiai, Shinya Sakai, Tatsuji Hirabayashi, Yukihiro Shimizu, Katsutoshi TerasawaAbstract:Abstract We studied the effect of Bafilomycin A1 (Baf-A1), a novel and highly specific inhibitor for vacuolar-type proton (V-H+) pump, on the growth of influenza A and B viruses in Madin-Darby canine kidney cells. Vital fluorescence microscopic study showed that Baf-A1 induced the complete disappearance of acidified compartments such as endosomes and lysosomes both in infected and uninfected cells by the treatment with 0.1 μM inhibitor for 1 h at 37°C. In addition, virus growth was inhibited when Baf-A1 was present from 1 h before infection to the end of incubation, or added within as early as 5–10 min after infection. Conversely, the virus growth was recovered in correlation with the reappearance of acidified compartments after removal of Baf-A1. These data suggest that Baf-A1-sensitive V-H+ pumps are solely responsible for the acidification of endosomes and lysosomes, and thus Baf-A1 inhibits the growth of influenza A and B viruses by affecting the acidified compartments in which low pH is essential for the uncoating process of influenza virus growth at an early stage of infection.
Carlo Farina - One of the best experts on this subject based on the ideXlab platform.
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chemistry and structure activity relationships of Bafilomycin A1 a potent and selective inhibitor of the vacuolar h atpase
Current Medicinal Chemistry, 1999Co-Authors: Stefania Gagliardi, M Rees, Carlo FarinaAbstract:Bafilomycin A1, a macrolide antibiotic isolated from the fermentation of Streptomyces spp., is a potent and selective inhibitor of vacuolar-type proton translocating ATP-ases (V-ATPases) and was used to study the physiological role of this class of enzymes. An extensive chemical effort on the unusual structure of this macrolide led to the synthesis of significantly different Bafilomycin derivatives. None of the new analogues was more potent than the parent compound but provided a significant amount of information about the structural requirements for the inhibitory activity of Bafilomycin A1 in particular on chicken osteoclast (cOc) ATPase. The vinylic methoxy group adjacent to a carbonyl function, the dienic system and the hydroxy group at position 7 were recognized to be essential features for Bafilomycin V-ATPase-inhibitory activity. This information was utilized to design simplified novel derivatives as inhibitors of bone resorption.
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synthesis and structure activity relationships of Bafilomycin A1 derivatives as inhibitors of vacuolar h atpase
Journal of Medicinal Chemistry, 1998Co-Authors: Stefania Gagliardi, P A Gatti, Pietro Belfiore, Andrea Zocchetti, Geoffrey D Clarke, Carlo FarinaAbstract:The macrolide antibiotic Bafilomycin A1 is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of Bafilomycin A1 were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of Bafilomycin A1. The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.
David Brough - One of the best experts on this subject based on the ideXlab platform.
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Bafilomycin A1 enhances nlrp3 inflammasome activation in human monocytes independent of lysosomal acidification
FEBS Journal, 2021Co-Authors: Jack Peter Green, Rose Wellens, Gloria Lopezcastejon, David BroughAbstract:The release of interleukin (IL)-1β from primary human monocytes in response to extracellular LPS occurs through the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. In primary monocytes, in response to LPS, NLRP3 inflammasome activation is characterized by an independence of K+ efflux and ASC speck formation and has been termed the 'alternative' pathway. Here, we report that pharmacological inhibition of V-ATPase with Bafilomycin A1 exacerbated LPS-induced NLRP3 inflammasome activation in primary human monocytes. Inhibition of V-ATPase in the presence of extracellular LPS led to NLRP3-dependent, K+ efflux-independent, ASC oligomerization and caspase-1 activation. Although V-ATPases are required for lysosomal acidification, we found that acidic lysosomal pH and protease activity were dispensable for this altered response, suggesting that V-ATPase inhibition triggered alternative signalling events. Therefore, V-ATPases may serve additional roles during NLRP3 inflammasome activation in primary human monocytes.
Kazuo Ohuchi - One of the best experts on this subject based on the ideXlab platform.
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Nitric Oxide Production by the Vacuolar-Type (H ϩ )-ATPase Inhibitors Bafilomycin A1 and Concanamycin A and Its Possible Role in Apoptosis in RAW 264.7 Cells
2020Co-Authors: Jangja Hong, Yasuhiro Nakano, Aya Yokomakura, Kenji Ishihara, Soon-joo Kim, Young-sook Kang, Kazuo Ohuchi, J H, S KAbstract:ABSTRACT In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type (H ϩ )-ATPase (V-ATPase) inhibitors Bafilomycin A1 and concanamycin A induced nitric oxide (NO) production through the expression of inducible nitric-oxide synthase mRNA and its protein and decreased cell growth and survival as determined by 3-(4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Bafilomycin A1 and concanamycin A activated nuclear factor (NF)-B and activator protein-1 and decreased the level of IB-␣ and increased that of phosphorylated c-Jun N-terminal kinase (JNK). NO production induced by these V-ATPase inhibitors was suppressed by the NF-B inhibitor Bay 11-7082 [(E)3-[(4-methylphenyl)sulfonyl])-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9-cd]pyrazol-6(2H)-one] in parallel with the partial alleviation of the V-ATPase inhibitor-induced decrease in MTT response. The Na ϩ ,K ϩ -ATPase inhibitor dibucaine and the F-ATPase inhibitor oligomycin did not induce NO production at which concentrations the MTT response was decreased. The NO donor Snitroso-N-acetyl-DL-penicillamine further lowered the V-ATPase inhibitor-induced decrease in the MTT response, and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (carboxy-PTIO) alleviated it partially. Mitochondrial depolarization, an index of apoptosis, was induced by Bafilomycin A1 and concanamycin A. On treatment with the nitric-oxide synthase inhibitor N G -monomethyl-L-arginine acetate, the disruption of mitochondrial membrane potential induced by Bafilomycin A1 and concanamycin A was alleviated partially in parallel with the decrease in NO production. Carboxy-PTIO also alleviated it partially. Our findings suggest that the V-ATPase inhibitors Bafilomycin A1 and concanamycin A similarly induce NO production and the newly produced NO participates partially in the V-ATPase inhibitorinduced apoptosis in RAW 264.7 cells
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Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors Bafilomycin A1 and concanamycin A and its possible role
2016Co-Authors: Jangja Hong, Yasuhiro Nakano, Aya Yokomakura, Kenji Ishihara, Soon-joo Kim, Young-sook Kang, Kazuo OhuchiAbstract:In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type (H)-ATPase (V-ATPase) inhibitors Bafilomycin A1 and concanamycin A induced nitric oxide (NO) production through the expression of inducible nitric-oxide synthase mRNA and its protein and decreased cell growth and survival as determined by 3-(4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltet-razolium bromide (MTT) assay. Bafilomycin A1 and concana-mycin A activated nuclear factor (NF)-B and activator pro-tein-1 and decreased the level of IB- and increased that of phosphorylated c-Jun N-terminal kinase (JNK). NO production induced by these V-ATPase inhibitors was suppressed by the NF-B inhibitor Bay 11-7082 [(E)3-[(4-methylphenyl)sulfonyl])-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9-cd]pyrazol-6(2H)-one] in parallel with the partial alleviation o
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increased production of reactive oxygen species by the vacuolar type h atpase inhibitors Bafilomycin A1 and concanamycin a in raw 264 cells
Journal of Toxicological Sciences, 2012Co-Authors: Aya Yokomakura, Jangja Hong, Kazuo Ohuchi, Jin-yong Lee, Nariyasu Mano, Tsutomu Takahashi, Gi-wook Hwang, Akira NaganumaAbstract:Treatment of the mouse leukemic cell line RAW 264 with Bafilomycin A1 or concanamycin A, inhibitors of vacuolar-type (H(+))-ATPases (V-ATPases), significantly increased the production of reactive oxygen species (ROS) and decreased cell viability. These effects were significantly suppressed by the presence of N-acetyl cysteine (NAC), an ROS scavenger. si-RNA mediated knockdown of the gene for the c subunit of the V0 domain of V-ATPase also resulted in an increase in ROS production and a decrease in cell viability. These results suggest that decreased cellular V-ATPase activity decreases cell viability by increasing ROS production in RAW 264 cells.
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Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors Bafilomycin A1 and concanamycin A and its possible role in apoptosis in RAW 264.7 cells.
The Journal of pharmacology and experimental therapeutics, 2006Co-Authors: Jangja Hong, Yasuhiro Nakano, Aya Yokomakura, Kenji Ishihara, Soon-joo Kim, Young-sook Kang, Kazuo OhuchiAbstract:In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type (H+)-ATPase (V-ATPase) inhibitors Bafilomycin A1 and concanamycin A induced nitric oxide (NO) production through the expression of inducible nitric-oxide synthase mRNA and its protein and decreased cell growth and survival as determined by 3-(4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Bafilomycin A1 and concanamycin A activated nuclear factor (NF)-κB and activator protein-1 and decreased the level of IκB-α and increased that of phosphorylated c-Jun N-terminal kinase (JNK). NO production induced by these V-ATPase inhibitors was suppressed by the NF-κB inhibitor Bay 11-7082 [( E )3-[(4-methylphenyl)sulfonyl])-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9- cd ]pyrazol-6(2 H )-one] in parallel with the partial alleviation of the V-ATPase inhibitor-induced decrease in MTT response. The Na+,K+-ATPase inhibitor dibucaine and the F-ATPase inhibitor oligomycin did not induce NO production at which concentrations the MTT response was decreased. The NO donor S -nitroso- N -acetyl-dl-penicillamine further lowered the V-ATPase inhibitor-induced decrease in the MTT response, and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (carboxy-PTIO) alleviated it partially. Mitochondrial depolarization, an index of apoptosis, was induced by Bafilomycin A1 and concanamycin A. On treatment with the nitric-oxide synthase inhibitor NG -monomethyl-l-arginine acetate, the disruption of mitochondrial membrane potential induced by Bafilomycin A1 and concanamycin A was alleviated partially in parallel with the decrease in NO production. Carboxy-PTIO also alleviated it partially. Our findings suggest that the V-ATPase inhibitors Bafilomycin A1 and concanamycin A similarly induce NO production and the newly produced NO participates partially in the V-ATPase inhibitor-induced apoptosis in RAW 264.7 cells.
Gloria Lopezcastejon - One of the best experts on this subject based on the ideXlab platform.
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Bafilomycin A1 enhances nlrp3 inflammasome activation in human monocytes independent of lysosomal acidification
FEBS Journal, 2021Co-Authors: Jack Peter Green, Rose Wellens, Gloria Lopezcastejon, David BroughAbstract:The release of interleukin (IL)-1β from primary human monocytes in response to extracellular LPS occurs through the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. In primary monocytes, in response to LPS, NLRP3 inflammasome activation is characterized by an independence of K+ efflux and ASC speck formation and has been termed the 'alternative' pathway. Here, we report that pharmacological inhibition of V-ATPase with Bafilomycin A1 exacerbated LPS-induced NLRP3 inflammasome activation in primary human monocytes. Inhibition of V-ATPase in the presence of extracellular LPS led to NLRP3-dependent, K+ efflux-independent, ASC oligomerization and caspase-1 activation. Although V-ATPases are required for lysosomal acidification, we found that acidic lysosomal pH and protease activity were dispensable for this altered response, suggesting that V-ATPase inhibition triggered alternative signalling events. Therefore, V-ATPases may serve additional roles during NLRP3 inflammasome activation in primary human monocytes.
