Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death

Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; Santos, Carlos Antônio do Nascimento; Campos, Andréa; Esteves, Ticiana Mota; Granjeiro, José Mauro

doi:10.1016/j.tiv.2015.02.010

Cited by 37 publications

(32 citation statements)

References 45 publications

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“…After exposure to secreted PS or TNFα, the levels of secreted mediators in culture supernatants were determined using the Luminex xMAP system, comprising a 27-Plex panel magnetic bead kit (for IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, bFGF, GCSF, GM-CSF, IFN-γ, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, PDGF-BB, RANTES, TNFα, VEGF), as previously described55. The concentration of each secreted product was estimated using the xPONENT software version 4.2 (Biorad Laboratories Inc., Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

The environmental yeast Cryptococcus liquefaciens produces capsular and secreted polysaccharides with similar pathogenic properties to those of C. neoformans

Araújo

Freitas

Fonseca

et al. 2017

Sci Rep

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Invasive fungal infections, including cryptococcosis, are a growing threat to immunocompromised patients. Although Cryptococcus neoformans and Cryptococcus gattii are the main agents of human cryptococcosis, opportunistic infections by environmental species, such as C. liquefaciens, have been observed recently. The main Cryptococcus virulence factor is the production and secretion of polysaccharides (PS). Previously, we showed that both species produce PS of similar composition. Here, we examined the ultrastructure and biological activity of capsular and secreted PS from C. liquefaciens, and yeast pathogenicity to an invertebrate host, in comparison with C. neoformans. Ultrastructural analysis by high-resolution microscopy showed that both species produce large and complex capsules. PS from both species had indistinguishable effects on phagocytosis levels, NO production and the secretion of a variety of immune mediators. Challenge with C. liquefaciens or C. neoformans led to complete lethality of G. mellonella larvae. Treatment with C. liquefaciens PS could not protect mice against infection with C. neoformans. We conclude that polysaccharides of the environmental yeast C. liquefaciens have strikingly similar ultrastructural and biological properties to those of C. neoformans, highlighting the importance of monitoring the emergence of new fungal pathogens for which thermotolerance may be an important transitional step towards pathogenesis in humans.

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Section: Methodsmentioning

confidence: 99%

The environmental yeast Cryptococcus liquefaciens produces capsular and secreted polysaccharides with similar pathogenic properties to those of C. neoformans

Araújo

Freitas

Fonseca

et al. 2017

Sci Rep

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“…A report has shown that AuNPs do not increase cytotoxicity in the ECs, but increase their susceptibility to cell death. 48 In this regard, the long-term effects of AuNPs on ECs need to be further investigated.…”

mentioning

confidence: 99%

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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“…We also observed that mPEG and PVP alone significantly increased necrotic cells. The influence of AuNPs on cell death and apoptosis has been documented previously, 9,12 including PEG-modified AuNPs, 41 whereby their accumulation in tissues after in vivo administration has also been shown to alter biochemical indices of liver and kidney damage 41 and upregulates markers of acute inflammation. 42 PVP-modified AuNPs have also been demonstrated to inhibit MMP activity without any cytotoxic effects.…”

mentioning

confidence: 76%

“…12,13 Furthermore, AuNPs can induce oxidative stress and generate reactive oxygen species, which can quench NO, thus affecting vascular function. 14,15 The cytotoxic effects of AuNPs have been shown to be dependent on cell type, NP size, shape, dosage, and in particular, surface chemistry.…”

Section: Introductionmentioning

confidence: 99%

Polyvinylpyrrolidone-coated gold nanoparticles inhibit endothelial cell viability, proliferation, and ERK1/2 phosphorylation and reduce the magnitude of endothelial-independent dilator responses in isolated aortic vessels

Mohamed¹,

Matou‐Nasri²,

Farooq³

et al. 2017

IJN

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Background Gold nanoparticles (AuNPs) demonstrate clinical potential for drug delivery and imaging diagnostics. As AuNPs aggregate in physiological fluids, polymer-surface modifications are utilized to allow their stabilization and enhance their retention time in blood. However, the impact of AuNPs on blood vessel function remains poorly understood. In the present study, we investigated the effects of AuNPs and their stabilizers on endothelial cell (EC) and vasodilator function. Materials and methods Citrate-stabilized AuNPs (12±3 nm) were synthesized and surface-modified using mercapto polyethylene glycol (mPEG) and polyvinylpyrrolidone (PVP) polymers. Their uptake by isolated ECs and whole vessels was visualized using transmission electron microscopy and quantified using inductively coupled plasma mass spectrometry. Their biological effects on EC proliferation, viability, apoptosis, and the ERK1/2-signaling pathway were determined using automated cell counting, flow cytometry, and Western blotting, respectively. Endothelial-dependent and independent vasodilator functions were assessed using isolated murine aortic vessel rings ex vivo. Results AuNPs were located in endothelial endosomes within 30 minutes’ exposure, while their surface modification delayed this cellular uptake over time. After 24 hours’ exposure, all AuNPs (including polymer-modified AuNPs) induced apoptosis and decreased cell viability/proliferation. These inhibitory effects were lost after 48 hours’ exposure (except for the PVP-modified AuNPs). Furthermore, all AuNPs decreased acetylcholine (ACh)-induced phosphorylation of ERK1/2, a key signaling protein of cell function. mPEG-modified AuNPs had lower cytostatic effects than PVP-modified AuNPs. Citrate-stabilized AuNPs did not alter endothelial-dependent vasodilation induced by ACh, but attenuated endothelial-independent responses induced by sodium nitroprusside. PVP-modified AuNPs attenuated ACh-induced dilation, whereas mPEG-modified AuNPs did not, though this was dose-related. Conclusion We demonstrated that mPEG-modified AuNPs at a therapeutic dosage showed lower cytostatic effects and were less detrimental to vasodilator function than PVP-modified AuNPs, indicating greater potential as agents for diagnostic imaging and therapy.

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Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death

Cited by 37 publications

References 45 publications

The environmental yeast Cryptococcus liquefaciens produces capsular and secreted polysaccharides with similar pathogenic properties to those of C. neoformans

The environmental yeast Cryptococcus liquefaciens produces capsular and secreted polysaccharides with similar pathogenic properties to those of C. neoformans

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

Polyvinylpyrrolidone-coated gold nanoparticles inhibit endothelial cell viability, proliferation, and ERK1/2 phosphorylation and reduce the magnitude of endothelial-independent dilator responses in isolated aortic vessels

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