title: Increased production of reactive oxygen species by the vacuolar-type (H(+))-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yokomakura
authors.forename: Jangja
authors.initials: J
authors.lastname: Hong
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohuchi
authors.forename: Seong-Eun
authors.initials: SE
authors.lastname: Oh
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D018942:Macrolides / Q000633:toxicity*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; D017382:Reactive Oxygen Species; C036978:concanamycin A; C040929:bafilomycin A1; D025262:Vacuolar Proton-Translocating ATPases