Insights into the impact of silver nanoparticles on human keratinocytes metabolism through NMR metabolomics

Carrola, Joana; Bastos, Verónica; Oliveira, José Miguel P. Ferreira de; Oliveira, Helena; Santos, Conceição; Gil, Ana M.; Duarte, Iola F.

doi:10.1016/j.abb.2015.08.022

Cited by 50 publications

(31 citation statements)

References 56 publications

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“…Sample Collection for Metabolomics : For metabolomics studies RAW 264.7 cells were seeded as detailed above and allowed to recover overnight. The cells were then exposed to low (10 µg mL −1 ) and high (500 µg mL −1 ) nanoparticle concentrations for up to 72 h. Cell extracts were prepared as detailed elsewhere . Briefly, at the desired time points, cells were placed on ice and kept at 4 °C throughout.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐co‐glycolic acid), and Silica Nanoparticles

Saborano

Wongpinyochit

Totten

et al. 2017

Adv Healthcare Materials

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Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic‐co‐glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications. 1H NMR analysis of cell extracts and culture media is used to quantify the changes in the intracellular and extracellular metabolomes of macrophages in response to nanoparticle exposure. Increased glycolytic activity, an altered tricarboxylic acid cycle, and reduced ATP generation are consistent with a proinflammatory phenotype. Furthermore, amino acids possibly arising from autophagy, the creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature is a common response to all nanoparticles tested; however, the direction and magnitude of some variations are clearly nanoparticle specific, indicating material‐induced biological specificity. Overall, metabolic reprogramming of macrophages can be achieved with nanoparticle treatments, modulated through the choice of the material, and monitored using 1H NMR metabolomics.

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Section: Methodsmentioning

confidence: 99%

Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐co‐glycolic acid), and Silica Nanoparticles

Saborano

Wongpinyochit

Totten

et al. 2017

Adv Healthcare Materials

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“…Metabolomics can generate much information about the relationship between nanomaterials and human cells. 27,37,38 Fig. S1 † shows the typical 1 H NMR spectrum of an aqueous extract from untreated HaCaT cells, our control experiment.…”

Section: Metabolomic Cell Profilementioning

confidence: 99%

Differential effects of graphene materials on the metabolism and function of human skin cells

et al. 2018

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Graphene-related materials (GRMs) such as graphene oxide (GO) and few-layer graphene (FLG) are used in multiple biomedical applications; however, there is still insufficient information available regarding their interactions with the main biological barriers such as skin. In this study, we explored the effects of GO and FLG on HaCaTs human skin keratinocytes, using NMR-based metabolomics and fluorescence microscopy to evaluate the global impact of each GRM on cell fate and damage. GO and FLG at low concentrations (5 μg mL-1) induced a differential remodeling of the metabolome, preceded by an increase in the level of radical oxygen species (ROS) and free cytosolic Ca2+. These changes are linked to a concentration-dependent increase in cell death by triggering apoptosis and necrosis, the latter being predominant at higher concentrations of the nanostructures. In addition, both compounds reduce the ability of HaCaT cells to heal wounds. Our results demonstrate that the GO and FLG used in this study, which mainly differ in their oxidation state, slightly trigger differential effects on HaCaTs cells, but with evident outcomes at the cellular and molecular levels. Their behavior as pro-apoptotic/necrotic substances and their ability to inhibit cell migration, even at low doses, should be considered in the development of future applications.

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“…A previous report clearly showed that both subchronic and acute dermal exposure of guinea pig to AgNPs could cause histopathologic abnormalities of skin tissue (Korani, Rezayat, Gilani, Arbabi Bidgoli, & Adeli, ). Notably, it is documented that AgNPs could cause an increase of the proinflammatory mediators’ release (Samberg, Oldenburg, & Monteiro‐Riviere, ) and induces metabolite change in skin cells (Carrola et al, ). These studies indicate that dermal exposure to AgNPs may cause distribution of these particles to skin, which might be a potential biological target organ for AgNPs.…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles increase connexin43‐mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen‐activated protein kinase signal pathway

Qin

Han

Yang

et al. 2017

J of Applied Toxicology

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Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to maintain tissue homeostasis. The aim of this study is to examine if non-coated AgNPs affect GJIC in human keratinocytes (HaCaT cells), and to identify the possible molecular mechanisms responsible for the effects. GJIC, connexin (Cx)43 protein and mRNA expression, and the effect of siRNA-mediated knockdown of Cx43 on GJIC were assessed. HaCaT cells exposed to non-coated AgNPs at different doses after a 24 hour exposure. To explore further the underlying mechanism, reactive oxygen species and mitogen-activated protein kinase pathway were evaluated after 2, 6, 12 and 24 hours. Our results revealed that non-coated AgNP exposure at subcytotoxic doses increase GJIC partially via Cx43 upregulation. Reactive oxygen species and extracellular signal-regulated kinase and activation of c-Jun N-terminal kinase were involved in the AgNP-induced upregulation of Cx43. This study provides new insight into the potential mechanism of AgNP biological activity.

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Insights into the impact of silver nanoparticles on human keratinocytes metabolism through NMR metabolomics

Cited by 50 publications

References 56 publications

Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐co‐glycolic acid), and Silica Nanoparticles

Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐co‐glycolic acid), and Silica Nanoparticles

Differential effects of graphene materials on the metabolism and function of human skin cells

Silver nanoparticles increase connexin43‐mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen‐activated protein kinase signal pathway

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