The Pentachlorophenol Metabolite Tetrachlorohydroquinone Induces Massive ROS and Prolonged p-ERK Expression in Splenocytes, Leading to Inhibition of Apoptosis and Necrotic Cell Death

Chen, Hsiu Min; Zhu, Ben Zhan; Chen, Rong Jane; Wang, Ying Jan

doi:10.1371/journal.pone.0089483

Cited by 14 publications

(18 citation statements)

References 89 publications

(88 reference statements)

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“…Arrest of cell cycling is usually observed in stressed cells, and it can result in apoptosis, necrosis, or both mechanisms simultaneously . It was reported that different types of ERK activation could lead to distinct cell death mechanisms, that is, apoptosis or necrosis . In this study, the expression of p‐ERK after exposure decreased in a time‐ and concentration‐dependent manner, indicating the presence of cell cycle arrest (Fig.…”

Section: Discussionsupporting

confidence: 49%

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Necrotic cell death caused by exposure to graphitic carbon‐coated magnetic nanoparticles

Kim

Sanetuntikul

Shanmugam

et al. 2015

J Biomedical Materials Res

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We synthesized graphitic carbon-coated magnetic nanoparticles (Fe@C NPs) and evaluated their physicochemical properties and mechanism of cytotoxicity in vitro. The structure of these nanocomposites consisted of an iron core encapsulated by a graphitic-carbon shell. The diameter of these Fe@C NPs was 81 ± 14 nm, and the thickness of the carbon layer encapsulating the core was 7.0 ± 0.5 nm. Inhibition of cell proliferation was induced by exposure to Fe@C NPs at doses above 50 μg mL(-1) . The exposed cells did not show increased activation of apoptosis biomarkers such as PARP, caspase-3, caspase-7, and caspase-9, and apoptosis-specific responses such as DNA laddering and annexin V binding to the cell membranes. In addition, the expression levels of autophagy-specific biomarkers such as ATG5 and LC3 after exposure were not enhanced, either. Instead, we observed increased release of lactate dehydrogenase in the culture media and red-fluorescent cell cytosol stained with ethidium homodimer I after the exposure. These results indicated enhanced cell membrane permeability after exposure to Fe@C NPs, probably caused by necrosis. The analysis of the regulatory molecules of cell cycling and proliferation, ERK, p53, and AKT, implied that cell cycle arrest was initiated and the cells were sensitized to necrosis. This necrotic cell death was also observed in carbon shells from Fe@C NPs obtained by removing the metal core. In conclusion, the graphitic carbon-encapsulated magnetic nanoparticles synthesized by one-pot synthesis induced necrotic cell death to human HEK293 cells, which was caused by graphitic carbon surface encapsulating the metal core.

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Section: Discussionsupporting

confidence: 49%

“…50 It was reported that different types of ERK activation could lead to distinct cell death mechanisms, that is, apoptosis or necrosis. 51 In this study, the expression of p-ERK after exposure decreased in a time-and concentration-dependent manner, indicating the presence of cell cycle arrest (Fig. 9).…”

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confidence: 56%

Necrotic cell death caused by exposure to graphitic carbon‐coated magnetic nanoparticles

Kim

Sanetuntikul

Shanmugam

et al. 2015

J Biomedical Materials Res

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“…Moreover, pretreatment with TCDD resulted in a time-dependent down-regulation of Bad and up-regulation of Bcl-xl and Bcl-2 after STS treatment ( Figure 3C ). Previous studies indicated loss of mitochondria membrane integrity is one of the early events leading to apoptosis [28] . To evaluate the effects of TCDD on preventing mitochondria membrane potential loss in response to STS, cells were pretreated with the fluorescent mitochondria staining dye DiOC 6 , and the changes of mitochondrial membrane potential were measured by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Membrane potential can be detected by incubation of cells with DiOC 6 . The interaction of mitochondria with DiOC6 is dependent on the stability of transmembrane potential and its uptake is reduced in apoptotic cells [28] . Therefore, apoptotic cells, with decreased mitochondrial membrane potential, showed reduced DiOC 6 fluorescence.…”

Section: Methodsmentioning

confidence: 99%

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

et al. 2014

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

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“…Exposure of HepG2 cells to 10 µM TCHQ produces significant amounts of reactive oxygen species (ROS) and decreases mitochondrial membrane potential ( 46 ). Exposure of primary splenocytes to 12.5 µM TCHQ produces ROS and substantially decreases viability ( 47 ). Treatment of hamster lung fibroblasts with 25 µM TCHQ for 1 h increases the level of 8-hydroxy-2-oxoguanosine, a marker of oxidative DNA damage, and induces single-strand breaks ( 48 ).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Analysis of Transcriptional Changes and Genes That Contribute to Fitness during Degradation of the Anthropogenic Pollutant Pentachlorophenol by Sphingobium chlorophenolicum

Flood

Copley

2018

mSystems

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Phenolic compounds such as pentachlorophenol (PCP), triclosan, and 2,4-dichlorophenoxyacetic acid (2,4-D) represent a common class of anthropogenic biocides. Despite the novelty of these compounds, many can be degraded by microbes isolated from contaminated sites. However, degradation of this class of chemicals often generates toxic intermediates, which may contribute to their recalcitrance to biodegradation. We have addressed the stresses associated with degradation of PCP by Sphingobium chlorophenolicum by examining the transcriptional response after PCP exposure and identifying genes necessary for growth during both exposure to and degradation of PCP. This work identifies some of the mechanisms that protect cells from this toxic compound and facilitate its degradation. This information could be used to engineer strains capable of improved biodegradation of PCP or similar phenolic pollutants.

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The Pentachlorophenol Metabolite Tetrachlorohydroquinone Induces Massive ROS and Prolonged p-ERK Expression in Splenocytes, Leading to Inhibition of Apoptosis and Necrotic Cell Death

Cited by 14 publications

References 89 publications

Necrotic cell death caused by exposure to graphitic carbon‐coated magnetic nanoparticles

Necrotic cell death caused by exposure to graphitic carbon‐coated magnetic nanoparticles

TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

Genome-Wide Analysis of Transcriptional Changes and Genes That Contribute to Fitness during Degradation of the Anthropogenic Pollutant Pentachlorophenol by Sphingobium chlorophenolicum

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