Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane

Orr, Galya; Panther, David; Cassens, Kaylyn J.; Phillips, Jaclyn L.; Tarasevich, Barbara J.; Pounds, Joel G.

doi:10.1016/j.taap.2009.01.022

Cited by 27 publications

(23 citation statements)

References 62 publications

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“…The specific cell surface molecules that participate in the recognition and internalization of ENPs, and their potential role in regulating inflammatory signals associated with toxicity, are poorly understood. Prior studies of ENP uptake mechanisms have primarily used pharmacological approaches to manipulate broad categories of cell internalization pathways, with more limited efforts made in identifying roles for specific receptors (Orr et al 2009) in the recognition and trafficking of ENPs. Nonetheless, future design of biocompatible ENPs for therapeutic use will need to consider specific biological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A

Orr¹,

Chrisler²,

Cassens³

et al. 2010

Nanotoxicology

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The cellular uptake of engineered nanoparticles (ENPs) is known to involve active transport mechanisms, yet the biological molecules involved are poorly understood. We demonstrate that the uptake of amorphous silica ENPs by macrophage cells, and the secretion of proinflammatory cytokines, is strongly inhibited by silencing expression of scavenger receptor A (SR-A). Conversely, ENP uptake is augmented by introducing SR-A expression into human cells that are normally non-phagocytic. Confocal microscopy analyses show that the majority of single or small clusters of silica ENPs co-localize with SR-A and are internalized through a pathway characteristic of clathrin-dependent endocytosis. In contrast, larger silica ENP agglomerates (>500 nm) are poorly co-localized with the receptor, suggesting that the physical agglomeration state of an ENP influences its cellular trafficking. As SR-A is expressed in macrophages throughout the reticulo-endothelial system, this pathway is likely an important determinant of the biological response to ENPs.

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Section: Introductionmentioning

confidence: 99%

Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A

Orr¹,

Chrisler²,

Cassens³

et al. 2010

Nanotoxicology

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“…In order to discriminate between attached and internalized lyophilisomes, a FITC quenching trypan blue assay was used [32]–[34]. Quenching of FITC signal occurs because trypan blue absorbs the light emitted by FITC-labeled lyophilisomes after excitation.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Cellular Uptake of Albumin-Based Lyophilisomes when Functionalized with Cell-Penetrating Peptide TAT in HeLa Cells

et al. 2014

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Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer capsules with potential use as drug delivery carrier. Cell-penetrating peptides (CPPs) including the TAT peptide have been successfully implemented for intracellular delivery of a broad variety of cargos including various nanoparticulate pharmaceutical carriers. In the present study, lyophilisomes were modified using CPPs in order to achieve enhanced cellular uptake. Lyophilisomes were prepared by a freezing, annealing, and lyophilization method and a cystein-elongated TAT peptide was conjugated to the lyophilisomes using a heterobifunctional linker. Fluorescent-activated cell sorting (FACS) was utilized to acquire a lyophilisome population with a particle diameter smaller than 1000 nm. Cultured HeLa, OVCAR-3, Caco-2 and SKOV-3 cells were exposed to unmodified lyophilisomes and TAT-conjugated lyophilisomes and examined with FACS. HeLa cells were investigated in more detail using a trypan blue quenching assay, confocal microscopy, and transmission electron microscopy. TAT-conjugation strongly increased binding and cellular uptake of lyophilisomes in a time-dependent manner in vitro, as assessed by FACS. These results were confirmed by confocal microscopy. Transmission electron microscopy indicated rapid cellular uptake of TAT-conjugated lyophilisomes via phagocytosis and/or macropinocytosis. In conclusion, TAT-peptides conjugated to albumin-based lyophilisomes are able to enhance cellular uptake of lyophilisomes in HeLa cells.

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“…Human mammary epithelial cells (HMEC) and mouse lung C10 cells were cultured as reported previously [15, 16]. These cells were treated with the adenoviruses as described for the HepG2 cells.…”

Section: Methodsmentioning

confidence: 99%

Reactive oxygen species alter autocrine and paracrine signaling

Zangar

Bollinger

Weber

et al. 2011

Free Radical Biology and Medicine

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Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine, and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endoplasmic reticulum has been poorly studied from the perspective of effects on cell biology. In this study, we express low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examine effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox sensitive dye, RedoxSensor Red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A custom ELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF) and vascular endothelial growth factor but suppressed secretion of CD14. The antioxidant, N-acetylcysteine, suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-κB pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

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Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane

Cited by 27 publications

References 62 publications

Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A

Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A

Enhanced Cellular Uptake of Albumin-Based Lyophilisomes when Functionalized with Cell-Penetrating Peptide TAT in HeLa Cells

Reactive oxygen species alter autocrine and paracrine signaling

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