Nuclear translocation of nuclear factor kappa B is regulated by G protein signaling pathway in arsenite-induced apoptosis in HBE cell line

Chen, Chengzhi; Gu, Shiyan; Jiang, Xuejun; Zhang, Zunzhen

doi:10.1002/tox.22183

Cited by 10 publications

(3 citation statements)

References 54 publications

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“…(a,b,f)]. These results were consistent with our previous work and other studies showing that the activation of NF‐κB signaling pathway was involved in arsenite‐induced apoptosis (Druwe and Vaillancourt, ; Chen et al, ). Importantly, our results also showed that regulation of Ca 2+ homeostasis in ER by heparin or thapsigargin was able to affect the nuclear translocation of NF‐κB [Fig.…”

Section: Discussionsupporting

confidence: 92%

Arsenite‐induced endoplasmic reticulum‐dependent apoptosis through disturbance of calcium homeostasis in HBE cell line

Chen

Jiang

et al. 2015

Environmental Toxicology

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Calcium (Ca ) is a ubiquitous cell signal responsible for multiple fundamental cellular functions, including apoptosis. Whether the homeostasis of Ca is involved in arsenite-induced apoptosis remains unclear. In this study, we observed that arsenite significantly elevated the intracellular Ca concentration in a dose- and time-dependent manner. By using the Ca -ATPase inhibitor, thapsigargin, and the inositol 1,4,5- trisphosphate receptors (IP3Rs) inhibitor, heparin, we further confirmed that the disturbance of endoplasmic reticulum (ER) Ca homeostasis caused Ca overload in the cells. Moreover, loss of ER Ca homeostasis also led to ER stress, mitochondrial dysfunction, and NF-κB activation. Importantly, pretreatment of cells with heparin remarkably attenuated the elevated cell apoptosis induced by arsenite, but inhibition of ER Ca uptake with thapsigargin exacerbated arsenite-induced cell damage significantly. Together, we demonstrated for the first time that arsenite disturbed the Ca homeostasis in ER, which subsequently led to ER stress, mitochondrial dysfunction, and NF-κB nuclear translocation, and thus consequently triggering cell apoptosis. Our findings indicate regulation of disrupted Ca homeostasis in ER may be a potential strategy for prevention of arsenite toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 197-216, 2017.

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Section: Discussionsupporting

confidence: 92%

Arsenite‐induced endoplasmic reticulum‐dependent apoptosis through disturbance of calcium homeostasis in HBE cell line

Chen

Jiang

et al. 2015

Environmental Toxicology

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“…The apoptotic effects of aspirin on HT29 cells have been reported to be mediated by NFκB activation [ 30 ]. NFκB activation has also been shown to increase cell death induced by antimitotic agents [ 31 ] and different agents, including ascorbyl stearate and arsenite, have been shown to induce cell death in cervical and 16-HBE cells respectively [ 32 , 33 ]. It has also been reported that the pro- or anti-apoptotic function of NFκB has been determined by the nature of the stimulation [ 34 ] and collectively, even if NFκB is best characterized for its protective activity as a response to proapoptotic stimulation, it can also induce programmed cell death in certain circumstances [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Food Additive Sodium Benzoate (NaB) Activates NFκB and Induces Apoptosis in HCT116 Cells

Yılmaz

Karabay

2018

Molecules

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NaB, the metabolite of cinnamon and sodium salt of benzoic acid is a commonly used food and beverage preservative. Various studies have investigated NaB for its effects on different cellular models. However, the effects of NaB on cancer cell viability signaling is substantially unknown. In this study, the effects of NaB on viability parameters and NFκB, one of the most important regulators in apoptosis, were examined in HCT116 colon cancer cells. Cell culture, light microscopy, spectrophotometry, flow cytometry, and western blot were used as methods to determine cell viability, caspase-3 activity, NFκB, Bcl-xl, Bim, and PARP proteins, respectively. NaB (6.25 mM–50 mM) treatment inhibited cell viability by inducing apoptosis, which was evident with increased Annexin V-PE staining and caspase-3 activity. NFκB activation accompanied the induction of apoptosis in NaB treated cells. Inhibition of NFκB with BAY 11-7082 did not show a pronounced effect on cell viability but induced a more apoptotic profile, which was confirmed by increased PARP fragmentation and caspase-3 activity. This effect was mostly evident at 50 mM concentration of NaB. Bcl-xl levels were not affected by NaB or BAY 11-7082/NaB treatment; whereas, total Bim increased with NaB treatment. Inhibition of NFκB activity further increased Bim levels. Overall, these results suggest that NaB induces apoptosis and activates NFκB in HCT116 colon cancer cells. Activation of NFκB emerges as target in an attempt to protect cells against apoptosis.

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“…Our previous work has shown that cell viability of HBE cells treated by arsenite was markedly reduced (Chen et al, ). In this study, we further examined arsenite cytotoxicity of HBE cells with a new sensitive and nontoxic assay, the Alamar blue assay.…”

Section: Resultsmentioning

confidence: 99%

Protection of Nrf2 against arsenite-induced oxidative damage is regulated by the cyclic guanosine monophosphate-protein kinase G signaling pathway

Chen

Jiang

et al. 2016

Environmental Toxicology

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Arsenite has been shown to induce a variety of oxidative damage in mammalian cells. However, the mechanisms underlying cellular responses to its adverse effects remain unknown. We previously showed that the level of Nrf2, a nuclear transcription factor significantly increased in arsenite-treated human bronchial epithelial (HBE) cells suggesting that Nrf2 is involved in responding to arsenite-induced oxidative damage. To explore how Nrf2 can impact arsenite-induced oxidative damage, in this study, we examined Nrf2 activation and its regulation upon cellular arsenite exposure as well as its effects on arsenite-induced oxidative damage in HBE cells. We found that Nrf2 mRNA and protein levels were significantly increased by arsenite in a dose- and time-dependent manner. Furthermore, we showed that over-expression of Nrf2 significantly reduced the level of arsenite-induced oxidative damage in HBE cells including DNA damage, chromosomal breakage, lipid peroxidation and depletion of antioxidants. This indicates a protective role of Nrf2 against arsenite toxicity. This was further supported by the fact that activation of Nrf2 by its agonists, tertiary butylhydroquinone (t-BHQ) and sulforaphane (SFN) resulted in the same protective effects against arsenite toxicity. Moreover, we demonstrated that arsenite-induced activation of Nrf2 was mediated by the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway. This is the first evidence showing that Nrf2 protects against arsenite-induced oxidative damage through the cGMP-PKG pathway. Our study suggests that activation of Nrf2 through the cGMP-PKG signaling pathway in HBE cells may be developed as a new strategy for prevention of arsenite toxicity.

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Nuclear translocation of nuclear factor kappa B is regulated by G protein signaling pathway in arsenite-induced apoptosis in HBE cell line

Cited by 10 publications

References 54 publications

Arsenite‐induced endoplasmic reticulum‐dependent apoptosis through disturbance of calcium homeostasis in HBE cell line

Arsenite‐induced endoplasmic reticulum‐dependent apoptosis through disturbance of calcium homeostasis in HBE cell line

Food Additive Sodium Benzoate (NaB) Activates NFκB and Induces Apoptosis in HCT116 Cells

Protection of Nrf2 against arsenite-induced oxidative damage is regulated by the cyclic guanosine monophosphate-protein kinase G signaling pathway

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