Effects of Silver Nanoparticles on Oxidative DNA Damage-repair as a Function of p38 MAPK Status: A Comparative Approach Using Human Jurkat T Cells and the Nematode Caenorhabditis elegans
Effects of Silver Nanoparticles on Oxidative DNA Damage-repair as a Function of p38 MAPK Status: A Comparative Approach Using Human Jurkat T Cells and the Nematode Caenorhabditis elegans
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DOI：
10.1002/em.21844
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发表时间：
2014-03-01
影响因子：
2.8
通讯作者：
Choi, Jinhee
中科院分区：
文献类型：
--
作者：
Chatterjee, Nivedita;Eom, Hyun Jeong;Choi, Jinhee
银纳米粒子(AgNPs)的大规模使用引起了人们对环境和人类健康潜在影响的担忧。我们以前曾报道，AgNP暴露会导致Jurkat T细胞和秀丽线虫体内活性氧增加，DNA损伤，并诱导p38MAPK和PMK-1的表达。为了阐明AgNP毒性的潜在机制，我们评估了AgNPs对DNA氧化损伤修复(人和线虫DNA糖基酶hOGG1、hNTH1、nth-1和8-oxo-GTPaseshMTH1、NDX-4)的影响，并探讨了p38MAPK和PMK-1在这一过程中的作用。我们的比较方法检测了野生型(WT)和p38MAPK敲除(KD)Jurkat T细胞(体外)以及WT和PMK-1功能丧失突变株(体内)的存活率、基因表达和酶活性。结果表明，p38MAPK/PMK-1对AgNP介导的毒性具有保护作用，AgNP处理的KD细胞存活率下降，PMK-1突变虫体内8OHdG积累量增加。此外，AgNP暴露后，hOGG1、hMTH1和NDX-4的表达和酶活性以及在NDX-4突变蠕虫中的存活率发生了剂量依赖性的变化。有趣的是，p38MAPK/PMK-1的缺失和缺失对AgNP诱导的NDX-4(Ok1003)、PMK-1(RNAi)突变体的存活、hOGG1和NDX-4的表达和酶活性产生了损伤和相加效应，这可能导致8OHdG的较高积累。综上所述，这些结果表明p38MAPK/PMK-1在AgNP诱导的DNA氧化损伤修复中起着重要的保护作用，这种损伤修复从线虫到人类都是保守的。环境。摩尔。诱变剂。2014年，55：122-133。(C)2013年威利期刊公司。
The large-scale use of silver nanoparticles (AgNPs) has raised concerns over potential impacts on the environment and human health. We previously reported that AgNP exposure causes an increase in reactive oxygen species, DNA damage, and induction of p38 MAPK and PMK-1 in Jurkat T cells and in Caenorhabditis elegans. To elucidate the underlying mechanisms of AgNP toxicity, here we evaluate the effects of AgNPs on oxidative DNA damage-repair (in human and C. elegans DNA glycosylases hOGG1, hNTH1, NTH-1, and 8-oxo-GTPaseshMTH1, NDX-4) and explore the role of p38 MAPK and PMK-1 in this process. Our comparative approach examined viability, gene expression, and enzyme activities in wild type (WT) and p38 MAPK knock-down (KD) Jurkat T cells (in vitro) and in WT and pmk-1 loss-of-function mutant strains of C. elegans (in vivo). The results suggest that p38 MAPK/PMK-1 plays protective role against AgNP-mediated toxicity, reduced viability and greater accumulation of 8OHdG was observed in AgNP-treated KD cells, and in pmk-1 mutant worms compared with their WT counterparts, respectively. Furthermore, dose-dependent alterations in hOGG1, hMTH1, and NDX-4 expression and enzyme activity, and survival in ndx-4 mutant worms occurred following AgNP exposure. Interestingly, the absence or depletion of p38 MAPK/PMK-1 caused impaired and additive effects in AgNP-induced ndx-4(ok1003); pmk-1(RNAi) mutant survival, and hOGG1 and NDX-4 expression and enzyme activity, which may lead to higher accumulation of 8OHdG. Together, the results indicate that p38 MAPK/PMK-1 plays an important protective role in AgNP-induced oxidative DNA damage-repair which is conserved from C. elegans to humans. Environ. Mol. Mutagen. 55:122-133, 2014. (c) 2013 Wiley Periodicals, Inc.