Cardoso 2017 Biochim Biophys Acta
|Cardoso GMF, Pletsch JT, Parmeggiani B, Grings M, Glanzel NM, Bobermin LD, Amaral AU, Wajner M, Leipnitz G (2017) Bioenergetics dysfunction, mitochondrial permeability transition pore opening and lipid peroxidation induced by hydrogen sulfide as relevant pathomechanisms underlying the neurological dysfunction characteristic of ethylmalonic encephalopathy. Biochim Biophys Acta 1863:2192-2201.|
Abstract: Hydrogen sulfide (sulfide) accumulates at high levels in brain of patients with ethylmalonic encephalopathy (EE). In the present study, we evaluated whether sulfide could disturb energy and redox homeostasis, and induce mitochondrial permeability transition (mPT) pore opening in rat brain aiming to better clarify the neuropathophysiology of EE. Sulfide decreased the activities of citrate synthase and aconitase in rat cerebral cortex mitochondria, and of creatine kinase (CK) in rat cerebral cortex, striatum and hippocampus supernatants. Glutathione prevented sulfide-induced CK activity decrease in the cerebral cortex. Sulfide also diminished mitochondrial respiration in cerebral cortex homogenates, and dissipated mitochondrial membrane potential (ΔΨm) and induced swelling in the presence of calcium in brain mitochondria. Alterations in ΔΨm and swelling caused by sulfide were prevented by the combination of ADP and cyclosporine A, and by ruthenium red, indicating the involvement of mPT in these effects. Furthermore, sulfide increased the levels of malondialdehyde in cerebral cortex supernatants, which was prevented by resveratrol and attenuated by glutathione, and of thiol groups in a medium devoid of brain samples. Finally, we verified that sulfide did not alter cell viability and DCFH oxidation in cerebral cortex slices, primary cortical astrocyte cultures and SH-SY5Y cells. Our data provide evidence that bioenergetics disturbance and lipid peroxidation along with mPT pore opening are involved in the pathophysiology of brain damage observed in EE.
Copyright © 2017 Elsevier B.V. All rights reserved. • Keywords: Bioenergetics, Mitochondrial permeability transition, Rat brain, Redox status, Sulfide, Amplex Red • Bioblast editor: Kandolf G • O2k-Network Lab: BR Porto Alegre Souza DOG
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology Pathology: Other Stress:Permeability transition Organism: Rat Tissue;cell: Nervous system Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS HRR: Oxygraph-2k, O2k-Fluorometer
2017-09, AmR, Resveratrol