1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells
1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells
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DOI：
10.1016/j.taap.2008.02.015
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发表时间：
2008-07-15
影响因子：
3.8
通讯作者：
Holme, Jorn A.
中科院分区：
文献类型：
--
作者：
Asare, Nana;Landvik, Nina E.;Holme, Jorn A.
对硝基多环芳烃（硝基多环芳烃）的机理研究可能有助于阐明哪些化学特性在引起毒性作用中最重要。1-硝基芘（I-NP）是柴油废气中主要的硝化多环芳烃。i - np暴露的Hepa1c1c7细胞表现出明显的细胞形态变化、增殖减少和不同形式的细胞死亡。暴露6 h后，细胞质空泡化显著增加，12 h时细胞开始聚集，24 h时细胞增殖率明显降低，出现凋亡和碘化丙啶（1,31）阳性细胞。电镜检查显示，空泡化的部分原因是线粒体肿胀。caspase抑制剂Z-VAD-FMK仅抑制凋亡细胞死亡，而Nec-l（一种坏死性凋亡抑制剂）对细胞死亡和空泡化均无抑制作用。相反，环己亚胺显著减少凋亡细胞和pi阳性细胞的数量以及细胞质空泡化，提示1-NP诱导paFaptOtiC细胞死亡。所有mapk；ERKII/2， p38和JNK似乎参与了死亡过程，因为在1-NP暴露时观察到明显的激活，并且它们的抑制剂部分减少了诱导的细胞死亡。ERK1/2抑制剂PD 98057完全阻断了诱导的空泡化，而其他MAPKs抑制剂对这一过程只有轻微的影响。提示1 -NP可能引起细胞凋亡和凋亡。相比之下，相应的胺（1-氨基芘）仅引起轻微的凋亡和坏死细胞死亡，并且没有典型的细胞凋亡特征。(c) 2008爱思唯尔公司版权所有。
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.