Amaral 2016 Biochim Biophys Acta: Difference between revisions
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|title=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< | |title=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<sup>2+</sup> 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. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/27240720 PMID: 27240720] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/27240720 PMID: 27240720 Open Access] | ||
|authors=Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M | |authors=Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M | ||
|year=2016 | |year=2016 | ||
|journal=Biochim Biophys Acta | |journal=Biochim Biophys Acta | ||
|abstract=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< | |abstract=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<sup>2+</sup> retention capacity in Ca<sup>2+</sup>-loaded brain and liver mitochondria. The reduction of Ca<sup>2+</sup> 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<sup>2+</sup>. 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 ยฉ 2016 Elsevier B.V. All rights reserved. | Copyright ยฉ 2016 Elsevier B.V. All rights reserved. | ||
|keywords=Medium-chain acyl-CoA dehydrogenase deficiency, Medium-chain acylcarnitines, Medium-chain fatty acids, Mitochondrial dysfunction, Mitochondrial permeability transition, Safranin | |keywords=Medium-chain acyl-CoA dehydrogenase deficiency, Medium-chain acylcarnitines, Medium-chain fatty acids, Mitochondrial dysfunction, Mitochondrial permeability transition, Safranin | ||
|mipnetlab=BR Porto Alegre | |mipnetlab=BR Porto Alegre Souza DOG | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, | |area=Respiration, Pharmacology;toxicology | ||
|injuries=Permeability transition, Oxidative stress;RONS | |||
|organism=Rat | |organism=Rat | ||
|tissues=Nervous system, Liver | |tissues=Nervous system, Liver | ||
|preparations= | |preparations=Isolated mitochondria | ||
|enzymes=Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase | |enzymes=Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase | ||
|topics=Inhibitor, Uncoupler, Fatty acid | |topics=Inhibitor, Uncoupler, Fatty acid | ||
|couplingstates=LEAK, OXPHOS, | |couplingstates=LEAK, OXPHOS, ET | ||
| | |pathways=N | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2016-07 | |additional=2016-07 | ||
}} | }} |
Latest revision as of 10:29, 10 June 2023
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 Ca2+ 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. |
Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M (2016) Biochim Biophys Acta
Abstract: 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 Ca2+ retention capacity in Ca2+-loaded brain and liver mitochondria. The reduction of Ca2+ 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 Ca2+. 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 ยฉ 2016 Elsevier B.V. All rights reserved. โข Keywords: Medium-chain acyl-CoA dehydrogenase deficiency, Medium-chain acylcarnitines, Medium-chain fatty acids, Mitochondrial dysfunction, Mitochondrial permeability transition, Safranin
โข O2k-Network Lab: BR Porto Alegre Souza DOG
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Permeability transition, Oxidative stress;RONS Organism: Rat Tissue;cell: Nervous system, Liver Preparation: Isolated mitochondria Enzyme: Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase Regulation: Inhibitor, Uncoupler, Fatty acid Coupling state: LEAK, OXPHOS, ET Pathway: N HRR: Oxygraph-2k
2016-07