Acrolein induces oxidative stress in brain mitochondria.
Acrolein, a byproduct of lipid peroxidation, has been shown to inflict significant structural and functional damage to isolated guinea pig spinal cord. Reactive oxygen species (ROS) are thought to mediate such detrimental effects. The current study demonstrates that acrolein can directly stimulate mitochondrial oxidative stress. Specifically, exposure of purified brain mitochondria to acrolein resulted in a dose-dependent increase of ROS and decreases in glutathione content and aconitase activity. This effect was not accompanied by significant intramitochondrial calcium influx or mitochondrial permeability transition, but rather by impaired function of the mitochondrial electron transport system. As well, we detected a significant inhibition of mitochondrial adenine nucleotide translocase (ANT) in the presence of acrolein. This inhibition of ANT likely contributes to acrolein-induced ROS elevation since application of atractyloside, a specific ANT inhibitor, induced significant increase of ROS. We hypothesize that inhibition of ANT may mediate, in part, the acrolein-induced ROS increase in mitochondria.
Luo
Jian
J
Department of Basic Medical Sciences, Institute for Applied Neurology, Center for Paralysis Research, Purdue University, West Lafayette, IN 47907, USA.
Shi
Riyi
R
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects
D005609:Free Radicals; D000171:Acrolein; D000226:Mitochondrial ADP, ATP Translocases; D002118:Calcium