API

Aop: 209

AOP Title

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Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP

Short name:

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Cholesterol and glutathione leading to hepatotoxicity: Multi-OMICS approach

Authors

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Jinhee Choi, Nivedita Chatterjee, Youngho Kim, Jae-Seong Jeong

Point of Contact

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Jinhee Choi

Contributors

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  • Jinhee Choi

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development


This AOP was last modified on February 15, 2017 04:17

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Revision dates for related pages

Page Revision Date/Time
Up Regulation, SREBF2 September 16, 2017 10:17
Up Regulation, Unsaturated fatty acid September 16, 2017 10:17
Down Regulation, GSS and GSTs gene September 16, 2017 10:17
Glutathione synthesis September 16, 2017 10:17
Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene September 16, 2017 10:17
Perturbation of cholesterol September 16, 2017 10:17
Glutathione homeostasis September 16, 2017 10:17
Hepatotoxicity February 15, 2017 04:11
Up Regulation, SREBF2 leads to Up Regulation, Unsaturated fatty acid February 15, 2017 04:11
Up Regulation, Unsaturated fatty acid leads to Perturbation of cholesterol February 15, 2017 04:12
Down Regulation, GSS and GSTs gene leads to Glutathione synthesis February 15, 2017 04:12
Glutathione synthesis leads to Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene February 15, 2017 04:12
Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene leads to Perturbation of cholesterol February 15, 2017 04:13
Down Regulation, GSS and GSTs gene leads to Glutathione homeostasis February 15, 2017 04:13
Perturbation of cholesterol leads to Hepatotoxicity February 15, 2017 04:13
Glutathione homeostasis leads to Hepatotoxicity February 15, 2017 04:13
Silica nanoparticles February 15, 2017 04:01

Abstract

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The system toxicology approach using ‘multi-OMICS-profiling-techniques’ (transcriptomics, proteomics and metabolomics) have proven to be robust tool for unraveling complex molecular machinery underlying various physiological, as well as, pathophysiological processes and have been successfully utilized in various fields including stress biology and toxicology. The application of multi-OMICS approaches are gaining acceptance in the regulatory community to provide information on a chemical’s hazard and risks though their mode-of-action (MOA), however, its utility in a AOP building context are still limited. This AOP is constituted the MIE as sterol regulatory element binding transcription factor 2 (SREBF2) gene activation and repressions of glutathione synthetase (GSS) and glutathione S-transferases (GSTA1, GSTA2, GSTA3, GSTA5) genes and the KEs as perturbation of cholesterol, though up regulated unsaturated fatty acid concentration, and glutathione homeostasis leading to oxidative stress, DNA damage and AO as hepatotoxicity (HepG2 cell death).


Background (optional)

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Summary of the AOP

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Stressors

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Name Evidence Term
Silica nanoparticles

Molecular Initiating Event

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Key Events

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Title Short name
Up Regulation, SREBF2 Up Regulation, SREBF2
Up Regulation, Unsaturated fatty acid Up Regulation, Unsaturated fatty acid
Down Regulation, GSS and GSTs gene Down Regulation, GSS and GSTs gene
Glutathione synthesis Glutathione synthesis
Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene
Perturbation of cholesterol Perturbation of cholesterol
Glutathione homeostasis Glutathione homeostasis

Adverse Outcome

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Title Short name
Hepatotoxicity Hepatotoxicity

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Life Stage Applicability

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Life stage Evidence
All life stages

Taxonomic Applicability

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Sex Applicability

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Sex Evidence
Unspecific

Graphical Representation

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Click to download graphical representation template

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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