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Key Event Title
Oxidative Stress in Brain
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 Do not cite|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
Oxidative stress is the imbalance between ROS and defence mechanisms against these ROS. Due to this imbalance the concentration of ROS can rise in the cells. The oxidizing free radicals can cause damage in the cell, at the DNA but also on multiple proteins. Nrf2 is an example of an defence mechanism against ROS.
How It Is Measured or Detected
One way to show oxidative stress in cells is to measure the ROS level. ROS generation can be determined in neuron cells. DHE, a small-molecule ROS probe, can be used for visualizing ROS generation with the use of an epifluorescence microscope. DHE is a direct way of measuring ROS, an indirect way is the measurement of glutathione depletion. The ratio between glutathione and oxidized glutathione can be determined, which shows indirectly whether the ROS level is increased. When oxidized glutathione is present in a higher concentration the ROS level is increased. Finally the expression level of Nrf2 can be determined in cells, with the use of a western blot analysis and antibodies for Nrf2. When the expression level of Nrf2 is much higher than in a control cell it indirectly shows that there is an increase in the concentration of ROS.
Domain of Applicability
Halpin, L. E., Collins, S. A. & Yamamoto, B. K. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sciences 97, 37–44 (2014).
Valencia-Olvera, A. C., Morán, J., Camacho-Carranza, R., Prospéro-García, O. & Espinosa-Aguirre, J. J. CYP2E1 induction leads to oxidative stress and cytotoxicity in glutathione-depleted cerebellar granule neurons. Toxicol. Vitr. 28, 1206–1214 (2014).
Nguyen, T., Nioi, P. & Pickett, C. B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 284, 13291–5 (2009).