Epigenetic mechanisms in nanomaterial-induced toxicity

Sudhaharan, Sukanya; Ng, Cheng Teng; Yung, Lin‐Yue Lanry; Dheen, S. Thameem; Bay, Boon Huat

doi:10.2217/epi.15.3

Cited by 59 publications

(59 citation statements)

References 127 publications

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“…Although reports on the alterations of the epigenetic integrity by nanoparticles are burgeoning, little efforts have been devoted to probe the impacts of AgNPs on histone modification [10]. Only one study previously reported a particular tropism for CdTe QDs in binding to histone, although no biological impacts were assessed Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Relative to a larger number of studies on genotoxic features of nanomaterials, only a few studies have been done to look into their capability to alter epigenetic integrity [10]. Considering the current reports on epigenetic alterations by nanomaterials, most studies were performed with focus on non-coding RNAs, such as miRNAs [10,11]. By contrast, very few studies have been carried out to assess histone modifications [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Considering the current reports on epigenetic alterations by nanomaterials, most studies were performed with focus on non-coding RNAs, such as miRNAs [10,11]. By contrast, very few studies have been carried out to assess histone modifications [10,11]. For example, gold nanoparticles and CdTe QDs were found to affect histone modifications, such as lysine methylation [12e14].…”

Section: Introductionmentioning

confidence: 99%

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Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

Qian

Zhang

et al. 2015

Biomaterials

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a b s t r a c tSilver nanoparticles (nanosilver, AgNPs) have been shown to induce toxicity in vitro and in vivo; however, the molecular bases underlying the detrimental effects have not been thoroughly understood. Although there are numerous studies on its genotoxicity, only a few studies have investigated the epigenetic changes, even less on the changes of histone modifications by AgNPs. In the current study, we probed the AgNP-induced alterations to histone methylation that could be responsible for globin reduction in erythroid cells. AgNP treatment caused a significant reduction of global methylation level for histone 3 (H3) in erythroid MEL cells at sublethal concentrations, devoid of oxidative stress. The ChIP-PCR analyses demonstrated that methylation of H3 at lysine (Lys) 4 (H3K4) and Lys 79 (H3K79) on the b-globin locus was greatly reduced. The reduction in methylation could be attributed to decreased histone methyltransferase DOT-1L and MLL levels as well as the direct binding between AgNPs to H3/H4 that provide steric hindrance to prevent methylation as predicted by the all-atom molecular dynamics simulations. This direct interaction was further proved by AgNP-mediated pull-down assay and immunoprecipitation assay. These changes, together with decreased RNA polymerase II activity and chromatin binding at this locus, resulted in decreased hemoglobin production. By contrast, Ag ion-treated cells showed no alterations in histone methylation level. Taken together, these results showed a novel finding in which AgNPs could alter the methylation status of histone. Our study therefore opens a new avenue to study the biological effects of AgNPs at sublethal concentrations from the perspective of epigenetic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

Qian

Zhang

et al. 2015

Biomaterials

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“…Transcriptional activity of a gene can be regulated by epigenetic processes, involving DNA methylation and histone modification and microRNAs(miRs) expression [29]. Lau et al demonstrated that after administration of a DNA methyltransferase inhibitor, the expression profile of AChE changed dramatically during the myogenesis process in C2C12 cells [30].…”

Section: Potential Roles Of Dna Methylation and Histone Modificationmentioning

confidence: 99%

New perspectives for multi-level regulations of neuronal acetylcholinesterase by dioxins

Xie

Chen

et al. 2016

Chemico-Biological Interactions

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a b s t r a c tAcetylcholinesterase (AChE; EC 3.1.1.7) is a vital functional enzyme in cholinergic neurotransmission which can rapidly hydrolyze neurotransmitter, acetylcholine, in the central and peripheral nervous systems. Emerging evidence showed that in addition to classical environmental AChE inhibitors, e.g. organophosphate and carbamate pesticides, dioxins are a new type of xenobiotic causing impairment of AChE. Dioxin can transcriptionally or post-transcriptionally suppress AChE expression in human neuroblastoma cells or mouse immune cells via the aryl hydrocarbon receptor (AhR) pathway, respectively. Dioxins can affect gene expression through other mechanisms, such as cross-talk with other signaling cascades and epigenetic modulations. Therefore, in this review, by summarizing the known mechanisms of AChE regulation and dioxin-induced gene alteration, potential signaling cascades and epigenetic mechanisms are proposed for dioxin-mediated AChE regulation. Mitogen activated protein (MAP) kinase, 3 0 , 5 0 -cyclic adenosine monophosphate (cAMP) and calcium-related singaling pathways, as well as potential epigenetic mechanisms, such as DNA methylation, and post-transcriptional regulation via microRNAs, including hsa-miR-132, hsa-miR-212 and hsa-miR-25-3p are discussed here. These proposed mechanisms may be invaluable not only to promote comprehensive understanding of the action mechanisms for dioxin, but to illustrate the molecular basis of dioxin-induced health impacts.

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“…In the era of "nano", we should not fear but control the use of nanomaterials. Cytotoxicity genotoxicity as well as possible toxicity due to epigenetic mechanisms should be focused in future studied [5]. …”

Section: Open Access Editorialmentioning

confidence: 99%