Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation
Autor: | Aurelia Vergeade, William E. Zackert, Taneem Amin, Sandra S. Zinkel, L. Jackson Roberts, Magdalena Bokiej, Qiong Shi, Huiyong Yin, Weizhen Ying, John A. Oates, Katherine Gruenberg, Olivier Boutaud, Tina S. Masterson |
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Rok vydání: | 2012 |
Předmět: |
Biochemistry & Molecular Biology
Cytochrome Cardiolipins Lipid peroxidation Biophysics Respiratory chain Cytochrome c Mitochondrion Medical Biochemistry and Metabolomics Biochemistry Article Catalysis chemistry.chemical_compound Medicinal and Biomolecular Chemistry Non-Narcotic Cardiolipin Humans Respiratory function Molecular Biology Acetaminophen Unsaturated Analgesics Arachidonic Acid biology Prevention digestive oral and skin physiology Fatty Acids Cytochromes c Redox cycling Cell Biology Analgesics Non-Narcotic Mitochondria chemistry 5.1 Pharmaceuticals Fatty Acids Unsaturated biology.protein lipids (amino acids peptides and proteins) Lipid Peroxidation Biochemistry and Cell Biology Development of treatments and therapeutic interventions Oxidation-Reduction Peroxidase |
Zdroj: | Biochemical and biophysical research communications, vol 423, iss 2 |
Popis: | Cytochrome (cyt) c can uncouple from the respiratory chain following mitochondrial stress and catalyze lipid peroxidation. Accumulating evidence shows that this phenomenon impairs mitochondrial respiratory function and also initiates the apoptotic cascade. Therefore, under certain conditions a pharmacological approach that can inhibit cyt c catalyzed lipid peroxidation may be beneficial. We recently showed that acetaminophen (ApAP) at normal pharmacologic concentrations can prevent hemoprotein-catalyzed lipid peroxidation in vitro and in vivo by reducing ferryl heme to its ferric state. We report here, for the first time, that ApAP inhibits cytochrome c-catalyzed oxidation of unsaturated free fatty acids and also the mitochondrial phospholipid, cardiolipin. Using isolated mitochondria, we also showed that ApAP inhibits cardiolipin oxidation induced by the pro-apoptotic protein, tBid. We found that the IC(50) of the inhibition of cardiolipin oxidation by ApAP is similar in both intact isolated mitochondria and cardiolipin liposomes, suggesting that ApAP penetrates well into the mitochondria. Together with our previous results, the findings presented herein suggest that ApAP is a pleiotropic inhibitor of peroxidase catalyzed lipid peroxidation. Our study also provides a potentially novel pharmacological approach for inhibiting the cascade of events that can result from redox cycling of cyt c. |
Databáze: | OpenAIRE |
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