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Aop: 207

AOP Title

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NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans

Short name:

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NADPH oxidase activation leading to reproductive failure

Graphical Representation

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Authors

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Jinhee Choi, University of Seoul, Republic of Korea

Nivedita Chatterjee, University of Seoul, India

Jaeseong Jeong, University of Seoul, Republic of Korea

Ji-yeon Roh, Knoell Korea, Republic of Korea

Point of Contact

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Jinhee Choi   (email point of contact)

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 Do not cite Under Development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 January 31, 2018 00:21

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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 January 21, 2018 21:07
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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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 1174 Activation, NADPH Oxidase Activation, NADPH Oxidase
2 KE 1278 ROS formation ROS formation
3 KE 1279 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK
4 KE 1280 Activation, HIF-1 Activation, HIF-1
5 KE 1281 Increased, DNA Damage-Repair Increased, DNA Damage-Repair
6 KE 176 Damaging, Mitochondria Damaging, Mitochondria
7 KE 1262 Apoptosis Apoptosis
8 AO 1277 Reproductive failure Reproductive failure

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Activation, NADPH Oxidase leads to ROS formation adjacent High
ROS formation leads to Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK adjacent High
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Increased, DNA Damage-Repair adjacent High
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Damaging, Mitochondria adjacent High
Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK leads to Activation, HIF-1 adjacent High
Activation, HIF-1 leads to Apoptosis adjacent High
Increased, DNA Damage-Repair leads to Apoptosis adjacent High
Damaging, Mitochondria leads to Apoptosis adjacent High
Apoptosis leads to Reproductive failure adjacent High

Network View

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Stressors

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Name Evidence Term
Silver nanoparticles High

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 High NCBI

Sex Applicability

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Sex Evidence
Unspecific

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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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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