Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells

Alazzam, Anas; Mfoumou, Etienne; Stiharu, Ion; Kassab, Amal; Darnel, Andrew D.; Yasmeen, Amber; Sivakumar, N.R.; Bhat, Rama; Moustafa, Ala‐Eddin Al

doi:10.1016/j.nano.2009.12.005

Cited by 30 publications

(22 citation statements)

References 30 publications

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“…Here, we investigated the role of the TGF-β receptor and its downstream Smad signaling components that regulate SM 22 -α expression in response to SWCNT induction of VAF differentiation into MFs. In support of other studies of the brain 20,21 and lung endothelial cells, 22,23 activation of the TGF-β receptor pathway was confirmed in our study that showed activation of the canonical Smad signaling pathway by an increase in Smad2/3 phosphorylation and decreased Smad7 levels. Our results showed that JNK was highly expressed instantly at an earlier stage (incubation with SWCNTs for 48 hours) but TGF-β1 expressed in both time-dependent and concentration-dependent manners which indicated that TGF-β1/Smads was the main signal pathway to modulate differentiation of VAFs into MFs induced by SWCNTs.…”

Section: Publish Your Work In This Journalsupporting

confidence: 92%

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression

Liu¹,

Liu²,

Xi³

et al. 2012

IJN

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Abstract:The aim of this study was to explore whether single-wall carbon nanotubes (SWCNTs) can be used as artery tissue-engineering materials by promoting vascular adventitial fibroblasts (VAFs) to transform into myofibroblasts (MFs) and to find the signal pathway involved in this process. VAFs were primary cultured and incubated with various doses of SWCNTs suspension (0, 0.8, 3.2, 12.5, 50, and 200 µg/mL). In the present study, we used three methods (MTT, WST-1, and WST-8) at the same time to detect the cell viability and immunofluorescence probe technology to investigate the effects of oxidative injury after VAFs incubated with SWCNTs. Immunocytochemical staining was used to detect SM 22 -α expression to confirm whether VAFs transformed into MFs. The protein levels were detected by western blotting. The results of immunocytochemical staining showed that SM 22 -α was expressed after incubation with 50 µg/mL SWCNTs for 96 hours, but with oxidative damage. The mRNA and protein levels of SM 22 -α, C-Jun N-terminal kinase, TGF-β 1 , and TGF-β receptor II in VAFs increased with the dose of SWCNTs. The expression of the p-Smad2/3 protein was upregulated while the Smad7 protein was significantly down-regulated. Smad4 was translocated to the nucleus to regulate SM 22 -α gene expression. In conclusion, SWCNTs promoted VAFs to transform into MFs with SM 22 -α expression by the C-Jun N-terminal kinase/Smads signal pathway at the early stage (48 hours) but weakened quickly. SWCNTs also promoted the transformation by the TGF-β l /Smads signal pathway at the advanced stage in a persistent manner. These results indicate that SWCNTs can possibly be used as artery tissue-engineering materials.

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Section: Publish Your Work In This Journalsupporting

confidence: 92%

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression

Liu¹,

Liu²,

Xi³

et al. 2012

IJN

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“…1). SWCNT exposure to various types of cells has been reported to stimulate a stress response at a concentration of 0.06 mg/mL for 24 h and at 0.1 mg/mL for 48 h. 11,14) Inconsistency between those studies and the present study may be attributed to the characteristics of the SWCNTs (length, diameter, purity of the nanotube, metal residue content, etc. ), exposure dose or time, or sensitivity of the cells to SWCNTs.…”

Section: Discussionsupporting

confidence: 46%

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

Hitoshi

Katoh

Suzuki

et al. 2012

Biological & Pharmaceutical Bulletin

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Carbon nanotubes (CNTs) are currently key promising materials of nanotechnology. However, elucidation of the possible effects of CNTs on the respiratory tract is urgently needed. The present study aimed to clarify the effect of single-walled CNTs (SWCNTs) on the expression of stress-responsive genes, using primary cultured normal human bronchial epithelial (NHBE), diseased HBE (DHBE) cells, and the human carcinoma cell lines A549 and FaDu. Purified SWCNTs were applied at concentrations of 0.1 or 1.0 mg/mL for 6 h, and a polymerase chain reaction (PCR) array was conducted to examine 84 stress-responsive genes. NHBE cell exposure to SWCNTs resulted in global downregulation of genes involved in inflammation, oxidative stress, and apoptosis. Further analysis using DHBE cells and carcinoma cell lines indicated a similar trend, although differences in sensitivity were observed. Downregulation of stress-responsive genes may be involved in the mechanism by which stress response protects against lung injury.Key words carbon nanotube; stress-responsive gene; human bronchial epithelial cell Nanotechnology has drastically emerged over the past 10 years, and a vast variety of nanomaterials, which can be employed in a wide range of applications in nanoscience, medicine, and engineering, have been created. Carbon nanotubes (CNTs), discovered by Iijima, are currently key promising materials of nanotechnology.

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“…Despite the potential advantages of SWCNTs as drug delivery carriers, there are many reports of their negative side effects such as cytotoxicity toward cultured cells, inhalation toxicity in animals, and effects on expression of genes involved in stress responses and apoptosis (Cui et al, 2005;Alazzam et al, 2010). These deleterious effects vary with the manufacturing method and the degree of purification to remove residual catalytic metals, which may also be toxicants.…”

Section: Introductionmentioning

confidence: 99%

Changes in Expression of Drug-Metabolizing Enzymes by Single-Walled Carbon Nanotubes in Human Respiratory Tract Cells

Hitoshi¹,

Katoh²,

Suzuki³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Single-walled carbon nanotubes (SWCNTs) have attracted attention for biomedical and biotechnological applications, such as drug delivery. However, there are concerns about the safety of SWCNTs for use in humans. To investigate the potential use of SWCNTs for targeted drug delivery to the lung, we examined their effect on drug-metabolizing enzymes in primary normal human bronchial epithelial (NHBE) cells from two donors and the lung carcinoma A549 cell line. Exposure of NHBE and A549 cells to SWCNTs dysregulated some of the important drug-metabolizing enzymes expressed in the human respiratory organs. Exposure of NHBE cells to SWCNTs for 24 h had a pronounced effect on expression of CYP1A1 and CYP1B1 mRNAs, which were reduced to less than 1% of control cells. These effects were also observed in A549 cells. Exposure of A549, HepG2 hepatic carcinoma cells, and MCF-7 breast carcinoma cells to tetrachlorodibenzo-p-dioxin induced the expression and enzymatic activity of CYP1A1 and CYP1B1, which were also suppressed by SWCNTs, suggesting that SWCNTs down-regulated both basal and induced CYP1A1 and CYP1B1 activities. Chromatin immunoprecipitation assays revealed that the down-regulatory effect of SWCNTs may be due to inhibition of activated aryl hydrocarbon receptor binding to the enhancer regions of the CYP1A1 and CYP1B1 genes. Down-regulation of CYP1A1 and CYP1B1 genes by SWCNTs may affect the defense mechanisms by reducing procarcinogen bioactivation in the human lung.

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Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells

Cited by 30 publications

References 30 publications

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

Changes in Expression of Drug-Metabolizing Enzymes by Single-Walled Carbon Nanotubes in Human Respiratory Tract Cells

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Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells

Cited by 30 publications

References 30 publications

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-&alpha; expression

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-&alpha; expression

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

Changes in Expression of Drug-Metabolizing Enzymes by Single-Walled Carbon Nanotubes in Human Respiratory Tract Cells

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Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression

Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression