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Key Event Title
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|
|CYP2E1 activation and formation of protein adducts leading to neurodegeneration||KeyEvent||Brendan Ferreri-Hanberry (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
Lipid peroxidation is the direct damage to lipids in the membrane of the cell or the membranes of the organelles inside the cells. Ultimately the membranes will break due to the build-up damage in the lipids This is mainly caused by oxidants which attack lipids specifically, since these contain carbon-carbon double bonds. During lipid peroxidation several lipid radicals are formed in a chain reaction. These reactions can interfere and stimulate each other. Antioxidants, such as vitamin E, can react with lipid peroxy radicals to prevent further damage in the cell. Main products of the lipid peroxidation reaction are lipid hydroperoxides, malondialdehyde and 4-hydroxynonenal.
How It Is Measured or Detected
Proteomics is a tool which can be used for the detection of 4-hydroxynonenal modified proteins. Mitochondrial and cytosolic proteins are subjected to 2D SDS-PAGE and are separated based on the size and pH. With the use of a polyclonal antibody against 4-hydroxynonenal which has an immunofluorescence tag the modified proteins can be detected. The proteins of interest on the SDS-PAGE gel can be cut out and cleaned. Cleaning is necessary since the identification is done by a MALDI-TOF MS analysis.
Domain of Applicability
Ayala, A., Muñoz, M. F. & Argüelles, S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity 2014, (2014)
Andringa, K. K., Udoh, U. S., Landar, A. & Bailey, S. M. Proteomic analysis of 4-hydroxynonenal (4-HNE) modified proteins in liver mitochondria from chronic ethanol-fed rats. Redox Biol. 2, 1038–1047 (2014)
Smathers, R. L., Galligan, J. J., Stewart, B. J. & Petersen, D. R. Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease. in Chemico-Biological Interactions 192, 107–112 (2011)