Acrolein, A Reactive Product of Lipid Peroxidation, Induces Oxidative Modification of Cytochrome c

Abstract

Jung Hoon KangDepartment of Genetic Engineering, Cheongju University, Cheongju 360-764, Korea. E-mail: jhkang@cju.ac.krReceived July 25, 2013, Accepted August 19, 2013Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids,which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). InAlzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stressis high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation withACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependentmanner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treatedcytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediatedcytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage ofcytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as acontributing factor to the pathology of AD.Key Words : Acrolein, Cytochrome c, Reactive oxygen species, IronIntroductionAcrolein (ACR) occurs in the environment as a ubiquitouspollutant that is generated as a by-product of overheatedorganic materials. ACR formed in vivo, through iron-cata-lyzed oxidation of arachidonic and docosahexanoic acids,exhibits facile reactivity with various biological macro-molecules, including proteins and phospholipids, has thepotential to inhibit many enzymes, and quickly depletescellular glutathione levels.