API

Event: 1585

Key Event Title

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Proteasomal dysfunction

Short name

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Proteasomal dysfunction

Biological Context

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Level of Biological Organization
Molecular

Cell term

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Organ term

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Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
α-diketone-induced bronchiolitis obliterans KeyEvent

Stressors

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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Key Event Description

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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

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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

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References

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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.