
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 284
Title
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
Short name
Graphical Representation
Contributors
- Frederic Y. Bois
Status
Author status | OECD status | OECD project | SAAOP status |
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Under development: Not open for comment. Do not cite |
This AOP was last modified on February 18, 2019 10:02
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Binding, Thiol/seleno-proteins involved in protection against oxidative stress | February 06, 2020 08:47 |
Oxidation, Glutathione (To be considered with MIE) | November 09, 2017 06:40 |
Decreased protection against oxidative stress | February 04, 2020 03:44 |
Oxidative Stress | March 12, 2020 14:26 |
Disruption, Mitochondrial electron transport chain | September 16, 2017 10:14 |
Increase, Cytotoxicity | September 16, 2017 10:16 |
Chronic kidney disease | February 18, 2019 09:58 |
Abstract
This AOP links thiol oxidation to CKD via oxidative and mitochondrial stress. Within the nephron, the proximal tubule is especially susceptible to injury from oxidative chemicals, as they can cause mitochondrial damage, which in turn can result in impairment of active and secondary transport, as well as in cell death. CKD is characterized by a progressive loss of renal function, the onset of which is initiated and/or accelerated by other factors such as diabetes, high blood pressure or exposure to nephrotoxic chemicals. Given its high energy demand for active transport, the proximal tubule is especially susceptible to injury from oxidative chemicals and mitotoxins.
Background (optional)
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
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1 | MIE | 1487 | Binding, Thiol/seleno-proteins involved in protection against oxidative stress | Binding, SH/SeH proteins involved in protection against oxidative stress |
2 | KE | 926 | Oxidation, Glutathione (To be considered with MIE) | Oxidation, Glutathione |
3 | KE | 1538 | Decreased protection against oxidative stress | Protection against oxidative stress, decreased |
4 | KE | 1392 | Oxidative Stress | Oxidative Stress |
5 | KE | 178 | Disruption, Mitochondrial electron transport chain | Disruption, Mitochondrial electron transport chain |
6 | KE | 768 | Increase, Cytotoxicity | Increase, Cytotoxicity |
7 | AO | 1603 | Chronic kidney disease | Chronic kidney disease |