title: Apoptosis induced by tungsten carbide-cobalt nanoparticles in JB6 cells involves ROS generation through both extrinsic and intrinsic apoptosis pathways.
abstract: In this study, apoptosis and related signaling induced by WC-Co nanoparticles were investigated in JB6 cells and rat lung macrophages. Electron spin resonance (ESR) and fluorescent staining indicated that both WC-Co nanoparticles and fine particles stimulated reactive oxygen species (ROS) generation. Catalase exhibited an inhibitory effect on WC-Co nanoparticle-induced ROS as well as mitochondrial membrane permeability damage. Further study indicated that WC-Co nanoparticles elicited higher cytotoxicity and apoptotic induction than fine particles. Western blot analysis showed activation of proapoptotic factors including Fas, Fas-associated protein with death domain (FADD), caspase 3, 8 and 9, BID and BAX. In addition, both cytochrome c and apoptosis-inducing factor (AIF) were upregulated and released from mitochondria to the cytoplasm. Our findings demonstrate that, on a mass basis, WC-Co nanoparticles exhibit higher cytotoxicity and apoptotic induction than fine particles. Apoptosis induced by WC-Co nanoparticles and fine particles involves both extrinsic and intrinsic apoptosis pathways.
authors: Department of Preventive Medicine of the Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China. zhaojinshun@nbu.edu.cn
authors: Jinshun
authors: J
authors: Zhao
authors: Linda
authors: L
authors: Bowman
authors: Ruth
authors: R
authors: Magaye
authors: Stephen S
authors: SS
authors: Leonard
authors: Vincent
authors: V
authors: Castranova
authors: Min
authors: M
authors: Ding
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D051336:Mitochondrial Membranes / Q000378:metabolism; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013499:Surface Properties; D017973:Tungsten Compounds / Q000633:toxicity*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000395:Air Pollutants, Occupational; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D002273:Carcinogens; C491899:Fas protein, mouse; C494830:AIFM1 protein, mouse; D017382:Reactive Oxygen Species; D017973:Tungsten Compounds; D019014:fas Receptor; C002802:tungsten carbide; D003035:Cobalt; D045304:Cytochromes c; D020169:Caspases