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Aop: 26

AOP Title

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Calcium-mediated neuronal ROS production and energy imbalance

Short name:

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Calcium-mediated neuronal ROS production and energy imbalance

Graphical Representation

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Click to download graphical representation template

Authors

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Point of Contact

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Lyle Burgoon   (email point of contact)

Contributors

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  • Lyle Burgoon
  • Erik Mylroie

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 Do not cite Under Development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 December 03, 2016 16:37

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Revision dates for related pages

Page Revision Date/Time
Inhibition, Ca++ ATPase September 16, 2017 10:14
Increase, Ca++ (intracellular) September 16, 2017 10:14
Disruption, Mitochondrial electron transport chain September 16, 2017 10:14
Decrease, Mitochondrial ATP production September 16, 2017 10:14
Increase, Reactive oxygen species production September 16, 2017 10:14
Decreased, Nitric Oxide September 16, 2017 10:14
Decreased, Long-term potentiation (LTP) September 16, 2017 10:14
Increased, Oxidative damage December 03, 2016 16:33
Inhibition, Ca++ ATPase leads to Increase, Ca++ (intracellular) December 03, 2016 16:37
Increase, Ca++ (intracellular) leads to Disruption, Mitochondrial electron transport chain December 03, 2016 16:37
Disruption, Mitochondrial electron transport chain leads to Decrease, Mitochondrial ATP production December 03, 2016 16:37
Disruption, Mitochondrial electron transport chain leads to Increase, ROS production December 03, 2016 16:37
Decreased, Nitric Oxide leads to Decreased, Long-term potentiation (LTP) December 03, 2016 16:37
Increase, ROS production leads to Decreased, Nitric Oxide December 03, 2016 16:37
Increase, ROS production leads to Increased, Oxidative damage December 03, 2016 16:37

Abstract

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Chemicals may lead to neurotoxicity through the inhibition of calcium ATPase activity, leading to increased intracellular calcium, increased ROS, and energy imbalance. This may lead to impaired nuerotransmission and oxidative neuronal damage.


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 51 Inhibition, Ca++ ATPase Inhibition, Ca++ ATPase
2 KE 50 Increase, Ca++ (intracellular) Increase, Ca++ (intracellular)
3 KE 178 Disruption, Mitochondrial electron transport chain Disruption, Mitochondrial electron transport chain
4 KE 40 Decrease, Mitochondrial ATP production Decrease, Mitochondrial ATP production
5 KE 257 Increase, Reactive oxygen species production Increase, ROS production
6 KE 193 Decreased, Nitric Oxide Decreased, Nitric Oxide
7 KE 166 Decreased, Long-term potentiation (LTP) Decreased, Long-term potentiation (LTP)
8 AO 356 Increased, Oxidative damage Increased, Oxidative damage

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Inhibition, Ca++ ATPase leads to Increase, Ca++ (intracellular) adjacent High
Increase, Ca++ (intracellular) leads to Disruption, Mitochondrial electron transport chain adjacent Moderate
Disruption, Mitochondrial electron transport chain leads to Decrease, Mitochondrial ATP production adjacent Moderate
Disruption, Mitochondrial electron transport chain leads to Increase, ROS production adjacent Moderate
Decreased, Nitric Oxide leads to Decreased, Long-term potentiation (LTP) adjacent Moderate
Increase, ROS production leads to Decreased, Nitric Oxide adjacent Low
Increase, ROS production leads to Increased, Oxidative damage adjacent High

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps.

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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