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Amaral 2016 Biochim Biophys Acta
Additional label 2016-07  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Enzyme Complex II;succinate dehydrogenase  + , Complex III  + , Complex IV;cytochrome c oxidase  + , Complex V;ATP synthase  +
Has abstract Medium-chain acyl-CoA dehydrogenase (MCAD)
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca<sub>2+</sub> retention capacity in Ca<sub>2+</sub>-loaded brain and liver mitochondria. The reduction of Ca<sub>2+</sub> retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca<sub>2+</sub>. Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. Copyright © 2016 Elsevier B.V. All rights reserved.
© 2016 Elsevier B.V. All rights reserved.  +
Has info [ PMID: 27240720]  +
Has publicationkeywords Medium-chain acyl-CoA dehydrogenase deficiency  + , Medium-chain acylcarnitines  + , Medium-chain fatty acids  + , Mitochondrial dysfunction  + , Mitochondrial permeability transition  + , Safranin  +
Has title Amaral AU, Cecatto C, da Silva JC, Wajner
Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M (2016) cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca<sub>2+</sub> homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency. Biochim Biophys Acta 1857:1363-72.
ciency. Biochim Biophys Acta 1857:1363-72.  +
Instrument and method Oxygraph-2k  +
Mammal and model Rat  +
MiP area Respiration  + , mt-Membrane  +
Pathways N  +
Preparation Permeabilized cells  + , Isolated mitochondria  +
Respiration and regulation Inhibitor  + , Uncoupler  + , Fatty acid  +
Tissue and cell Nervous system  + , Liver  +
Was published by MiPNetLab BR Porto Alegre Klamt F +
Was published in journal Biochim Biophys Acta +
Was published in year 2016  +
Was written by Amaral AU + , Cecatto C + , Da Silva JC + , Wajner A + , Godoy KD + , Ribeiro RT + , Wajner M +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
13:30:45, 9 November 2017  +
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