Aminoacetone induces iron-mediated oxidative damage to isolated rat liver mitochondria

Archives of Biochemistry and Biophysics
Fernando Dutra, Etelvino J H Bechara

Abstract

Aminoacetone (AA) is a threonine metabolite accumulated in threoninemia, cri-du-chat, and diabetes, where it contributes toward the formation of cytotoxic and genotoxic methylglyoxal (MG). Oxyradicals yielded from iron-catalyzed AA aerobic oxidation to MG are shown here to promote Ca2+ -mediated mitochondrial membrane permeabilization in an AA dose-dependent way. The inhibitory effect of added EGTA, cyclosporin A, Mg2+, and DTT observed in this study suggests the formation of transition pores in the inner mitochondrial membrane by AA, associated with thiol protein aggregation. That the mitochondrial iron pool plays a coadjutant role in the transition of mitochondrial permeability is indicated by the dramatic inhibitory effect of added o-phenanthroline. Iron released from ferritin by AA oxidation products--superoxide anion and AA enolyl radicals--is shown to act as an alternative source of ferrous iron, intensifying the mitochondrial damage. These findings may contribute to clarify the role of accumulated AA and iron overload in the mitochondrial oxidative damage reportedly occurring in diabetes mellitus.

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Citations

Sep 24, 2008·Journal of Molecular Evolution·Xiang Jia Min, Donal A Hickey
Jun 19, 2008·American Journal of Physiology. Endocrinology and Metabolism·Krisztian StadlerMaria B Kadiiska
Jun 7, 2008·Drug Metabolism and Drug Interactions·David L Vander Jagt
Apr 15, 2016·Pharmacognosy Magazine·Sivakumar Thasma RamanZhongzheng Gui
Jan 1, 2008·Chemico-biological Interactions·Miklós Péter Kalapos
Apr 17, 2008·International Journal of Cancer. Journal International Du Cancer·Daniel PouliquenJean Menanteau
Sep 17, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Daniel Y HungMichael S Roberts
Feb 27, 2021·Free Radical Biology & Medicine·Luiz D RamosEtelvino J H Bechara
Jun 4, 2020·Heliyon·Xu-Yan YangShuai-Nan Zhang

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