1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells

被引:44
|
作者
Asare, Nana [1 ]
Landvik, Nina E. [1 ]
Lagadic-Gossmann, Dominique [2 ,3 ]
Rissel, Mary [2 ,3 ]
Tekpli, Xavier [2 ,3 ]
Ask, Kjetil [4 ]
Lag, Marit [1 ]
Holme, Jorn A. [1 ]
机构
[1] Norwegian Inst Publ Hlth, Div Environm Med, N-0403 Oslo, Norway
[2] Grp Toxic Environm Contaminants Iabellisee Ligue, INSERM U620, F-35043 Rennes, France
[3] Univ Rennes 1, IFR 140, F-35043 Rennes, France
[4] McMaster Univ, Dept Pathol & Mol Med, Ctr Gene Therapeut, Hamilton, ON, Canada
关键词
1-nitropyrene; 1-aminopyrene; apoptosis; paraptosis; cell signaling;
D O I
10.1016/j.taap.2008.02.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mechanistic studies of nitro-PAHs (polycyclic aromatic hydrocarbons) of interest might help elucidate which chemical characteristics are most important in eliciting toxic effects. 1-Nitropyrene (I-NP) is the predominant nitrated PAH emitted in diesel exhaust. I-NP-exposed Hepa1c1c7 cells exhibited marked changes in cellular morphology, decreased proliferation and different forms of cell death. A dramatic increase in cytoplasmic vacuolization was observed already after 6 h of exposure and the cells started to round up at 12 h. The rate of cell proliferation was markedly reduced at 24 h and apoptotic as well as propidiurn iodide (1,31)-positive cells appeared. Electron microscopic examination revealed that the vacuolization was partly due to mitochondria swelling. The caspase inhibitor Z-VAD-FMK inhibited only the apoptotic cell death and Nec-l (an inhibitor of necroptosis) exhibited no inhibitory effects on either cell death or vacuolization. In contrast, cycloheximide markedly reduced both the number of apoptotic and PI-positive cells as well as the cytoplasmic vacuolization, suggesting that 1-NP induced paFaptOtiC cell death. All the MAPKs; ERKII/2, p38 and JNK, appear to be involved in the death Process since marked activation was observed upon 1-NP exposure, and their inhibitors partly reduced the induced cell death. The ERK1/2 inhibitor PD 98057 completely blocked the induced vacuolization, whereas the other MAPKs inhibitors only had minor effects on this process. These findings suggest that 1 -NP may cause apoptosis and paraptosis. In contrast, the corresponding amine (1-aminopyrene) elicited only minor apoptotic and necrotic cell death, and cells with characteristics typical of paraptosis vvere absent. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:175 / 186
页数:12
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