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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Diversity in Cell Signaling Responses01:22

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The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
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Overview of Cell Signaling01:23

Overview of Cell Signaling

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Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate with the environment.
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Amplifying Signals via Second Messengers01:15

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Intracellular Signaling Cascades01:24

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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Related Experiment Video

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Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
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Signaling Pathways Regulated by Silica Nanoparticles.

Shih-Yi Hsu1, Robert Morris1, Feng Cheng1

  • 1Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.

Molecules (Basel, Switzerland)
|April 3, 2021
PubMed
Summary

Silica nanoparticles, used in drug delivery, can cause toxic effects. This study reveals common TNF and MAPK signaling pathway activation in human cells exposed to these nanoparticles, suggesting a toxicity mechanism.

Keywords:
NCBI GEOgene pathwaymechanismmicroarraynanomaterialsilicon dioxide

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Area of Science:

  • Nanotechnology
  • Toxicology
  • Molecular Biology

Background:

  • Silica nanoparticles are widely used in drug and gene delivery systems.
  • While their applications are growing, the molecular mechanisms of silica nanoparticle toxicity are not well understood.
  • Existing risk management tools do not fully address the potential health impacts.

Purpose of the Study:

  • To investigate the toxic effects of silica nanoparticle exposure on human cells.
  • To elucidate the molecular mechanisms underlying silica nanoparticle-induced toxicity.
  • To identify common cellular responses across different human cell types.

Main Methods:

  • Toxicogenomic analysis was employed to study cellular responses.
  • Three distinct human cell lines were used: human aortic endothelial cells, mouse-derived macrophages, and A549 non-small cell lung cancer cells.
  • Gene expression patterns were analyzed to identify affected biological pathways.

Main Results:

  • Silica nanoparticle exposure led to the upregulation of specific signaling pathways in all tested cell types.
  • The Tumor Necrosis Factor (TNF) signaling pathway was commonly affected.
  • The Mitogen-Activated Protein Kinase (MAPK) signaling pathway was also commonly upregulated across the cell lines.
  • These pathways are critical in cellular stress responses and inflammation.

Conclusions:

  • Silica nanoparticle exposure commonly upregulates TNF and MAPK signaling pathways in human aortic endothelial cells, macrophages, and lung cancer cells.
  • These findings provide insights into the potential molecular mechanisms of silica nanoparticle toxicity in vivo.
  • Further research is warranted to fully understand and mitigate the health risks associated with silica nanoparticle exposure.