Reactive gamma-ketoaldehydes formed via the isoprostane pathway disrupt mitochondrial respiration and calcium homeostasis.

ABSTRACT: Isoketals (IsoKs) are gamma-ketoaldehydes formed via the isoprostane pathway of arachidonic acid peroxidation and are among the most reactive by-products of lipid peroxidation. IsoKs selectively adduct to protein lysine residues and are highly cytotoxic, but the targets and molecular events involved in IsoK-induced cell death are poorly defined. Our previous work established that physiologically relevant aldehydes induce mitochondrial dysfunction (Kristal et al., J. Biol. Chem.271:6033-6038; 1996). We therefore examined whether IsoKs induced mitochondrial dysfunction. Incubation of mitochondria with synthetic IsoKs in the presence or absence of Ca(2+) was associated with alterations in mitochondrial respiration, membrane potential (DeltaPsi), and pyridine nucleotide redox state. IsoKs dose

SUBMITTER: Stavrovskaya IG 

PROVIDER: S-EPMC2903647 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature