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Event: 2081

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased Modified Proteins

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Modified Proteins
Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Deposition of energy leading to cataracts KeyEvent Vinita Chauhan (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens Moderate NCBI
mouse Mus musculus Low NCBI
rat Rattus norvegicus Moderate NCBI
bovine Bos taurus Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Juvenile Moderate
Adult Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Male Moderate
Female Low
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Proteins are considered to be modified following any change in structural components, as well as protein levels. Modifications to proteins can occur at any one of the structural levels of proteins, primary structure (amino acid or polypeptide sequence), the secondary structure (alpha helix or beta sheet structures), or the tertiary structure (globular protein forms). Protein modifications can include post-translational modifications such as deamidation, oxidation, carbonylation, etc. Protein structure specificity can be crucial to their ability to execute their functional duties within a cell. Protein modifications can in turn affect protein-protein interactions, potentially hindering the ability to perform those functions. These affected protein interactions can result in unfolding, aggregation, insolubility, and increased molecular weight (Toyoma et al., 2013; Young, 1994). This can lead to the development of various age-related diseases, such as cataracts. As an example, modification of the tertiary structure of lens crystallin proteins can cause protein aggregation, increased lens opacity, and eventually cataracts (Moreau & King, 2012).  

Modified proteins also refers to changes in protein levels which can result from changes in how proteins are synthesized (through transcription and translation), modified, and regulated in cells. These processes are governed spatially and temporally by transcriptional and translational regulators as well as other signaling moieties and are tightly linked to the functional needs of cells, which can change depending on the presence of stressors or other external signaling factors. Misregulation of protein expression can trigger a cascade of changes in downstream intracellular activities, which can then cause abnormal cellular dynamics. This misregulation can include abnormally high or low levels of particular proteins or even abnormalities in their breakdown.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Listed below are common methods for detecting the KE, however there may be other comparable methods that are not listed. 

Method of Measurement  

References  

Description  

OECD-Approved Assay  

Mass Spectrometry  

(Noble & Bailey, 2009)  

Technique involves measuring the mass-to-charge ratio of ions to identify and quantify molecules and architectural changes such as the post-translational modifications of proteins  

No 

Proximity Ligation Assay 

(Noble & Bailey, 2009)  

An immunohistochemical tool that can help perform in situ detection of endogenous proteins, protein modifications, and protein interactions with high specificity and sensitivity 

No 

Western Blot 

(Noble & Bailey, 2009)  

Immunoblotting technique using antibody to detect its antigen and can be used for measuring protein levels.  

No 

Bicinchoninic Acid Assay (BCA) 

(Noble & Bailey, 2009)  

Can assist in quantification of total protein in a sample with colorimetric changes propagated through proteins mediated reduction of Cu+2 to Cu+1.  

No 

A280(Spectroscopy) 

(Noble & Bailey, 2009)  

Direct assay method for protein concentration determination in solution through measuring absorbance at 280 nm.  

No 

Lowry Assay 

(Noble & Bailey, 2009)  

Binding of administered agents to proteins causes measurable spectral shift to the blue form of the dye which can be used to quantify protein-levels. 

No 

Protein Mass Spectrometry  

(Noble & Bailey, 2009)  

Proteins initially digested various recombinant proteases, most often trypsin and are then subsequently observed at the tandem mass spectrometer (MS1) as a series of peaks, each with a different mass-to-charge ratio.  

No 

ELISA 

(Alomari et al. 2018) 

Carbonyl content on proteins detected using a plate reader following chromogenic reaction 

No 

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxonomic applicability: Modified proteins are applicable to all animals as proteins exist in some form in the cells of all animals (Cray, 2012).  

Life stage applicability: This key event is not life stage specific as individuals in all life stages have proteins that can be modified (Dalle-Donne et al., 2006; Krisko & Radman, 2019). However, older individuals have naturally higher baseline levels of modified proteins, and those levels can even be used to determine an individual’s age (Krisko & Radman, 2019). 

Sex applicability: This key event is not sex specific as both sexes have proteins that can be modified. Evidence shows that males have a slightly higher level of protein carbonylation than their age-matched female counterparts (Barreiro et al., 2006). 

Evidence for perturbation by a stressor: There is evidence to demonstrate that protein modification can occur as a result of multiple stressor types including oxidizing agents and ionizing & non-ionizing radiation (Hightower, 1995, Hamada et al., 2014; Lipman et al., 1988; Reisz et al., 2014).  

References

List of the literature that was cited for this KE description. More help

Alomari, E. et al. (2018), “Protein carbonylation detection methods: A comparison”, Data in Brief, Vol.19, Elsevier, Amsterdam, https://doi.org/10.1016/j.dib.2018.06.088. 

Barreiro, E. et al. (2006), “Aging, sex differences, and oxidative stress in human respiratory and limb muscles”, Free Radical Biology & Medicine, Vol.41/5, Elsevier, Amsterdam, https://doi.org/10.1016/j.freeradbiomed.2006.05.027. 

Cray, C. (2012), “Chapter 5 - Acute Phase Proteins in Animals”, Progress in Molecular Biology and Translational Science, Vol.105, Elsevier, Amsterdam, https://doi.org/10.1016/B978-0-12-394596-9.00005-6. 

Dalle-Donne, I. et al. (2006), “Protein carbonylation, cellular dysfunction, and disease progression”, Journal of Cellular and Molecular Medicine, Vol.10/2, Wiley-Blackwell, Hoboken, https://doi.org/10.1111/j.1582-4934.2006.tb00407.x. 

Hamada, N. et al. (2014), “Emerging issues in radiogenic cataracts and cardiovascular disease”, Journal of Radiation Research, Vol.55/5, Oxford University Press, Oxford, https://doi.org/10.1093/jrr/rru036.  

Hightower, K. (1995), “The role of the Lens epithelium in development of UV cataract”, Current Eye Research, Vol.14/1, Taylor & Francis, Oxfordshire, https://doi.org/10.3109/02713689508999916. 

Krisko, A. and M. Radman. (2019), “Protein damage, ageing and age-related diseases”, Open Biology, 9/3, The Royal Society, London, https://doi.org/10.1098/rsob.180249. 

Lipman, R., B. Tripathi and R. Tripathi. (1988), “Cataracts induced by microwave and ionizing radiation”, Survey of Ophthalmology, Vol.33/3, Elsevier, Amsterdam, https://doi.org/10.1016/0039-6257(88)90088-4. 

Moreau, K. L. and J. A. King (2012), “Protein misfolding and aggregation in cataract disease and prospects for prevention”, Trends in Molecular Medicine, Vol. 18/5, Elsevier Ltd, England, https://doi.org/10.1016/j.molmed.2012.03.005 

Reisz, J. et al. (2014), “Effects of ionizing radiation on biological molecules - mechanisms of damage and emerging methods of detection”, Antioxidants and Redox Signaling, Vol.21(2), Mary Ann Liebert Inc, Larchmont, https://doi.org/10.1089/ars.2013.5489.  

Noble, J. E., & Bailey, M. J. A. (2009). Chapter 8 Quantitation of Protein. In Methods in Enzymology (Vol. 463, Issue C, pp. 73–95). Academic Press Inc.  

Toyama, B., & Hetzer, M. (2013). Protein homeostasis: Live long, won't prosper. Nature Reviews Molecular Cell Biology, 14(1), pp.55-61. 

Young, R. (1994). The family of sunlight-related eye diseases. Optometry and Vision Science, 71(2), pp.125-144.