title: Molecular mechanisms involved in the adaptive response to cadmium-induced apoptosis in human myelomonocytic lymphoma U937 cells.
abstract: We examined the molecular mechanisms involved in the adaptive response to cadmium (Cd)-induced apoptosis in human myelomonocytic lymphoma U937 cells. When U937 cells were treated with 50 μM cadmium chloride (CdCl2) for 12 h, significant apoptosis occurred. This was associated with an increase in intracellular reactive oxygen species (ROS), sustained phosphorylation of JNK, activation of caspase-3, a decrease in Mcl-1 (anti-apoptotic Bcl-2 proteins), and increases in Bim, Noxa and tBid (a pro-apoptotic protein under the Bcl-2 family). No apoptosis occurred when the cells were treated with 1 μM CdCl2 for 72 h. However, pretreatment with low-dose CdCl2 dramatically altered the sensitivity of the cells to 50 μM CdCl2 with inhibition of apoptosis. Concomitantly, there were significant decreases in the generation of intracellular ROS and the activation of JNK. Pretreatment with 1 μM CdCl2 also attenuated the decrease in Mcl-1 and the increases in Bim, Noxa and tBid induced by 50 μM CdCl2. In conclusion, pretreatment with low-dose Cd inhibited apoptosis induced by high-dose Cd. The mechanism involves inhibition of intracellular ROS generation and JNK activation, and modulating the balance between the expression of Mcl-1 and its binding partners, Bim, Noxa and tBid.
authors.affiliation: Department of Public Health, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Zheng-Guo
authors.initials: ZG
authors.lastname: Cui
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ogawa
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Piao
authors.forename: Kei
authors.initials: K
authors.lastname: Hamazaki
authors.forename: Loreto B
authors.initials: LB
authors.lastname: Feril
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Hidekuni
authors.initials: H
authors.lastname: Inadera
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells
chemical_list: D004785:Environmental Pollutants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases