API

Aop: 207

AOP Title

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NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans : Case study on silver nanoparticle

Short name:

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NADPH oxidase activation leading to reproductive failure

Authors

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Jinhee Choi, Nivedita Chatterjee, 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 Do not cite Under Development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 03:40

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Revision dates for related pages

Page Revision Date/Time
Activation, NADPH Oxidase September 16, 2017 10:17
Reproductive failure February 15, 2017 03:18
ROS formation September 16, 2017 10:17
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK September 16, 2017 10:17
Activation, HIF-1 September 16, 2017 10:17
Increased, DNA Damage-Repair September 16, 2017 10:17
Damaging, Mitochondria September 27, 2017 16:05
Apoptosis February 07, 2017 13:21
Activation, NADPH Oxidase leads to ROS formation February 15, 2017 03:31
ROS formation leads to Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK February 15, 2017 03:31
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Increased, DNA Damage-Repair February 15, 2017 03:32
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Damaging, Mitochondria February 15, 2017 03:32
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Activation, HIF-1 February 15, 2017 03:32
Activation, HIF-1 leads to Apoptosis February 15, 2017 03:32
Increased, DNA Damage-Repair leads to Apoptosis February 15, 2017 03:33
Damaging, Mitochondria leads to Apoptosis February 15, 2017 03:33
Apoptosis leads to Reproductive failure February 15, 2017 03:33
Silver nanoparticles February 15, 2017 03:19

Abstract

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NADPH oxidases are proteins that transfer electrons across biological membranes. The biological function of this enzymes is the generation of reactive oxygen species(ROS). ROS may be involved in mediation of apoptosis via variety cellular effects like oxidative stress, DNA damage and mitochondrial damage, and finally lead to reproductive failure. This AOP is constituted the MIE as NADPH oxidase activation, KEs as Reactive Oxygen Species (ROS) formation, oxidative stress, mitochondrial damage, DNA damage and apoptosis, and AO as reproductive failure. Silver nanoparticles (AgNPs) are used as stressor. To experimentally validate the link between MIE, KEs and AO, C. elegans functional genetic tools are used. C. elegans functional mutants involved in each MIE and KE, such as, bli-3  (NADPH Oxidase), pmk-1 (P38 MAPK), hif-1 (Transcription factor), fmo-2 (Effector), cyp35a2 (Effector), sod-3 (Effector), nth-1 (DNA damage/repair) and ndx-4 (DNA damage/repair).


Background (optional)

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Summary of the AOP

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Stressors

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Name Evidence Term
Silver nanoparticles Strong

Molecular Initiating Event

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Title Short name
Activation, NADPH Oxidase Activation, NADPH Oxidase

Key Events

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Title Short name
ROS formation ROS formation
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK
Activation, HIF-1 Activation, HIF-1
Increased, DNA Damage-Repair Increased, DNA Damage-Repair
Damaging, Mitochondria Damaging, Mitochondria
Apoptosis Apoptosis

Adverse Outcome

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Title Short name
Reproductive failure Reproductive failure

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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Term Scientific Term Evidence Link
Caenorhabditis elegans Caenorhabditis elegans Strong NCBI

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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