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AOP: 207
Title
NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
Short name
Graphical Representation
Point of Contact
Contributors
- Jinhee Choi
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on June 03, 2024 21:02
Revision dates for related pages
Page | Revision Date/Time |
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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 |
Apoptosis | February 28, 2024 09:40 |
Mitochondrial dysfunction | April 17, 2024 08:26 |
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 Mitochondrial dysfunction | March 14, 2024 12:10 |
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 |
Mitochondrial dysfunction leads to Apoptosis | March 13, 2024 14:59 |
Apoptosis leads to Reproductive failure | February 15, 2017 03:33 |
Silver nanoparticles | February 15, 2017 03:19 |
Abstract
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).
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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MIE | 1174 | Activation, NADPH Oxidase | Activation, NADPH Oxidase |
KE | 1278 | ROS formation | ROS formation |
KE | 1279 | Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK | Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK |
KE | 1280 | Activation, HIF-1 | Activation, HIF-1 |
KE | 1281 | Increased, DNA Damage-Repair | Increased, DNA Damage-Repair |
KE | 177 | Mitochondrial dysfunction | Mitochondrial dysfunction |
KE | 1262 | Apoptosis | Apoptosis |
AO | 1277 | Reproductive failure | Reproductive failure |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Prototypical Stressors
Name |
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Silver nanoparticles |
Life Stage Applicability
Life stage | Evidence |
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All life stages |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
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Caenorhabditis elegans | Caenorhabditis elegans | High | NCBI |
Sex Applicability
Sex | Evidence |
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Unspecific |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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