Relationship:948

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Key Event Relationship Overview

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Description of Relationship

Upstream Event Downstream Event/Outcome
Oxidative Stress, Increase Glutathione, Oxidation

AOPs Referencing Relationship

AOP Name Type of Relationship Weight of Evidence Quantitative Understanding
Oxidative Stress Leading to Arterial Stiffness Directly Leads to Strong Moderate

Taxonomic Applicability

Name Scientific Name Evidence Links
Homo sapiens Homo sapiens Strong NCBI
Bos taurus Bos taurus NCBI
Rattus norvegicus Rattus norvegicus NCBI

How Does This Key Event Relationship Work

Under physiological conditions, glutathione (GSH) functions as an anti-oxidant by defending the cell from products of oxidative stress (Kalinina et al., 2014). It is predominantly found in the reduced form while the oxidized form glutathione disulfide (GSSG) generally does not exceed 1% of its total cellular context. Exposure to oxidants like peroxides leads to the oxidation of intracellular reduced GSH, resulting in the formation of GSSG which alters the redox state of the cell (Pullar et al., 2001). This imbalance in GSH/GSSG ratio is a marker of oxidative stress and contributes to endothelial dysfunction.

Weight of Evidence

Biological Plausibility

Empirical Support for Linkage

Include consideration of temporal concordance here

Uncertainties or Inconsistencies

Quantitative Understanding of the Linkage

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Evidence Supporting Taxonomic Applicability

References