Mechanistic study on the biological effects of silver and gold nanoparticles in Caco-2 cells – Induction of the Nrf2/HO-1 pathway by high concentrations of silver nanoparticles

Aueviriyavit, Sasitorn; Phummiratch, Duangkamol; Maniratanachote, Rawiwan

doi:10.1016/j.toxlet.2013.09.020

Cited by 103 publications

(93 citation statements)

References 54 publications

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“…[44][45][46] Furthermore, some AuNPs and silver nanoparticles are able to induce HO-1 expression by causing cytotoxicity and oxidative stress. 19,20,47 However, the AuNPs in this study caused Nrf2 activation and HO-1 expression in a short incubation. The TEM analysis revealed that some AuNPs were located in the cytoplasm at 2 hours of treatment (data not shown), suggesting that the uptake of AuNPs by ECs can be an early event.…”

mentioning

confidence: 53%

“…18 However, some studies have also shown that nanoparticles, particularly high concentrations of silver nanoparticles, exhibit cell cytotoxicity and, therefore, induce HO-1 expression. 19,20 In our parallel study, we observed that AuNPs are able to inhibit cell adhesion molecule (CAM) expression and have anti-inflammatory effects on human vascular ECs (unpublished data). Given that HO-1 expression has been associated with anti-inflammation and injury in some tissues, 6 we hypothesized that AuNPs can affect HO-1 expression.…”

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confidence: 87%

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Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Lai¹,

Shieh²,

Tsou³

et al. 2015

IJN

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It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. The induction was reduced by the thiol-containing antioxidants, including N-acetylcysteine and glutathione, but not by the non-thiol-containing antioxidants and inhibitors that block the enzymes for intracellular reactive oxygen species generation. The AuNPs enhanced Nrf2 protein levels but did not affect Nrf2 mRNA expression. In response to the AuNP treatment, the cytosolic Nrf2 translocated to the nucleus, and, concomitantly, Bach1 exited the nucleus and its tyrosine phosphorylation increased. The chromatin immunoprecipitation assay revealed that the translocated Nrf2 bound to the antioxidant-response element located in the E2 enhancer region of the HO-1 gene promoter and acted as a transcription factor. Although N-acetylcysteine inhibited the AuNP-induced Nrf2 nuclear translocation, the AuNPs did not promote intracellular reactive oxygen species production or endoplasmic reticulum stress in the ECs. Knockdown of Nrf2 expression by RNA interference significantly inhibited AuNP-induced HO-1 expression at the protein and mRNA levels. In summary, AuNPs enhance the levels and nuclear translocation of the Nrf2 protein and Bach1 export/tyrosine phosphorylation, leading to Nrf2 binding to the HO-1 E2 enhancer promoter region to drive HO-1 expression in ECs. This study, together with our parallel findings, demonstrates that AuNPs can act as an HO-1 inducer, which may partially contribute to their anti-inflammatory bioactivity in human vascular ECs.

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confidence: 53%

mentioning

confidence: 87%

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Lai¹,

Shieh²,

Tsou³

et al. 2015

IJN

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“…In contrast to our results, AgNPs (15 µg/mL) elevated Nrf2 mRNA (approximately 1.8-fold) and protein levels in Caco-2 cells, a human colorectal adenocarcinoma cell line, 3 and 6 hours, respectively. 36 The previous study found elevated Nrf2 protein levels in the nuclear fraction after normalization of nuclear Nrf2 with GAPDH protein levels. 36 In another report of rainbow trout (Oncorhynchus mykiss) hepatocytes, 10 µg/mL AgNPs with an average size of 9 nm stimulated glycogenolysis and reduced PEPCK activity 48 hours after treatment.…”

Section: Discussionmentioning

confidence: 91%

“…36 The previous study found elevated Nrf2 protein levels in the nuclear fraction after normalization of nuclear Nrf2 with GAPDH protein levels. 36 In another report of rainbow trout (Oncorhynchus mykiss) hepatocytes, 10 µg/mL AgNPs with an average size of 9 nm stimulated glycogenolysis and reduced PEPCK activity 48 hours after treatment. 37 It was not clear whether the alterations in Nrf2 and PEPCK expression were direct effects or were secondary results due to compensation for metabolic changes caused by AgNPs.…”

Section: Discussionmentioning

confidence: 91%

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Lee

Lee²,

Yun³

et al. 2015

IJN

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The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS.

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“…[11][12][13] Studies in intestinal epithelial cell models have reported Ag NP toxicity including decreased cell viability, formation of reactive oxygen species (ROS), decreased mitochondrial function, increased IL-8 generation by cells, and DNA damage. [14][15][16][17] However, there has been less thorough investigation of the mechanism of Ag NP toxicity in intestinal epithelial models and no investigation of Ag NP effects on cell proliferation. It is known that oxidative stress plays a role in inflammation and disease progression in the intestines, so an increase in oxidative stress by Ag NP in the intestines may be particularly problematic for those with intestinal pathologies.…”

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confidence: 99%

Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation by silver nanoparticles

McCracken

Zane

Knight

et al. 2015

Toxicology in Vitro

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Abstract:Use of silver nanoparticles (NP) is of interest in the food and food packaging industries for their antimicrobial properties. In order to investigate potential consequences of Ag NP ingestion, this study was performed in the intestinal epithelial cell line C2BBe1. Ag NP were synthesized and characterized prior to biological experiments. The Ag NP had an average diameter of 23 nm as determined by TEM analysis. treated with up to 10 µg/cm 2 (50 µg/mL) Ag NP, suggesting that these cells are not as sensitive to Ag NP. This is likely due to exposure of each cell to a smaller number of Ag NP when the cells are confluent in addition to decreased metabolic activity and increased resistance to toxic agents in confluent cells. Based on these studies, Ag NP ingestion may be able to slow proliferation of 3 stem cells of the intestinal crypt and this is something that needs to be investigated further. The largest effects may be seen in diseased intestines where the epithelium is compromised. 4Introduction:

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Mechanistic study on the biological effects of silver and gold nanoparticles in Caco-2 cells – Induction of the Nrf2/HO-1 pathway by high concentrations of silver nanoparticles

Cited by 103 publications

References 54 publications

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation by silver nanoparticles

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