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Event: 1585
Key Event Title
Proteasomal dysfunction
Short name
Biological Context
Level of Biological Organization |
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Molecular |
Cell term
Organ term
Key Event Components
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
α-diketone-induced bronchiolitis obliterans | KeyEvent | Marvin Martens (send email) | Under development: Not open for comment. Do not cite | |
Calcium overload driven development of parkinsonian motor deficits | KeyEvent | Julia Meerman (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Life Stages
Sex Applicability
Key Event Description
The covalent interaction of α-diketones with arginines leads to altered structure and functioning of proteins. Indication of widespread protein damage was observed in DA exposed mice (Hubbs et al. 2016)
How It Is Measured or Detected
The inactivation of enzymes due to the interaction of α-diketones with arginine residues at their active sites has been demonstrated (Chen and Chen 2003). Protein damage has been measured by accumulation of ubiquitin and sequestosome-1 in the lungs of exposed mice (Hubbs et al. 2016)
Domain of Applicability
References
Chen, G., Chen, X., 2003. Arginine residues in the active site of human phenol sulfotransferase (SULT1A1). J. Biol. Chem. 278, 36358–36364.
Hubbs, A. F., Fluharty, K. L., Edwards, R. J., Barnabei, J. L., Grantham, J. T., Palmer, S. M., … Sriram, K. (2016). Accumulation of Ubiquitin and Sequestosome-1 Implicate Protein Damage in Diacetyl-Induced Cytotoxicity. In American Journal of Pathology (Vol. 186, pp. 2887–2908). https://doi.org/10.1016/j.ajpath.2016.07.018
More, S.S., et al., 2012a. The butter flavorant, diacetyl, forms a covalent adduct with 2-deoxyguanosine, uncoils DNA, and leads to cell death. J. Agric. Food Chem. 60, 3311–3317.