The accumulation of assembly intermediates of the mitochondrial complex I matrix arm is reduced by limiting glucose uptake in a neuronal-like model of MELAS syndrome

Ketogenic diet (KD) which combined carbohydrate restriction and the addition of ketone bodies has emerged as an alternative metabolic intervention used as an anticonvulsant therapy or to treat different types of neurological or mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation. The broad success of KD is due to multiple beneficial mechanisms with distinct effects of very low carbohydrates and ketones. To evaluate the metabolic part of carbohydrate restriction, transmitochondrial neuronal-like cybrid cells carrying the m.3243A > G mutation, shown to be associated with a severe complex I deficiency was exposed during 3 weeks to glucose restriction. Mitochondrial enzyme defects were combined with an accumulation of complex I (CI) matrix intermediates in the untreated mutant cells, leading to a drastic reduction in CI driven respiration. The severe reduction of CI was also paralleled in post-mortem brain tissue of a MELAS patient carrying high mutant load. Importantly, lowering significantly glucose concentration in cell culture improved CI assembly with a significant reduction of matrix assembly intermediates and respiration capacities were restored in a sequential manner. In addition, OXPHOS protein expression and mitochondrial DNA copy number were significantly increased in mutant cells exposed to glucose restriction. The accumulation of CI matrix intermediates appeared as a hallmark of MELAS pathophysiology highlighting a critical pathophysiological mechanism involving CI disassembly, which can be alleviated by lowering glucose fuelling and the induction of mitochondrial biogenesis, emphasizing the usefulness of metabolic interventions in MELAS syndrome

Impact of Sulforaphane and PhytonutrianceTM Broccoli extract on Helicobacter pylori and Campylobacter jejuni.

Poste

Electrooxidation of porphyrin free bases: Fate of the π-cation radical

International audienceIn contrast to metalloporphyrins with non-electroactive metal centres, the π-cation radicals of porphyrin free bases (H2OEP, H2TPP, H2CdiE) electrogenerated in strictly anhydrous solvents are not stable and give rise to a quantitative chemical reaction. Conjunction of electrochemical and spectroscopic data (UV/VIS, EPR and NMR) demonstrates unambiguously that the porphyrin skeleton is not modified during the chemical reaction. The reaction product is the protonated free base, and thus the free base can be regenerated by reduction of the protons

Reactivity toward dioxygen of dicobalt face-to-face diporphyrins in aprotic media. Experimental and theoretical aspects. Possible mechanistic implication in the reduction of dioxygen

International audienceThe reactivity toward dioxygen of two series of dicobalt cofacial diporphyrins in solution in an aprotic solvent is described. Some of these compounds are efficient electrocatalysts for the four-electron reduction of dioxygen when adsorbed on a graphite electrode immersed in aqueous acid. Their electrochemical and spectroscopic (UV-vis, EPR) behavior in solution shows that, contrary to what is observed with cobalt monomers, the neutral [PCo(II) Co(II)P] (1) (P stands for a porphyrin ring) form does not react with dioxygen. Uniquely the one- and two-electron-oxidized forms of the dimer, [PCo(II)·Co(II)P]+ (1+) and [PCo(II)−-Co(II)P]2+ (12+), respectively, reversibly bind dioxygen, giving two complexes. 2 and 3, at room temperature and in the absence of a good axial ligand. The stability constants of the two O2 complexes have been measured spectrophotometrically and/or electrochemically, and prove to be remarkably high. As a whole, the present O2 binding processes appear unprecedented as basically different in many respects from the process classically described in the case of cobalt monomers. Extended Huckel molecular orbital (EHMO) calculations, based on the crystal structure of the Co2FTF4 dimer in its uncomplexed form (Co-Co distance 3.42 Å), show that, in the absence of very important deformations of its structure, the only possible geometry for the O2 complex of the two- electron-oxidized derivative [PCo-O2-CoP]2+ (3) is the μ-η2:η2- peroxo structure. The calculated corresponding electronic diagram affords a rationale for most of the experimentally observed properties. Specifically, the O2 complex of the one-electron-oxidized form [PCo-O2·-CoP]+ (2), the reduced form of complex 3, should be considered as a species in which the O2 moiety is further reduced, at least partially, as compared to its peroxo state in 3, i.e., consequently in an oxidation state intermediate between peroxo (-1) and oxo (-2). Preliminary results indicate that this species reacts with one proton, while the two-electron-oxidized O2 complex 3 is resistant to protonation. The possible implications of these specific properties of the dicobalt dimers in the four-electron reduction mechanism of O2 are discussed, and structural and mechanistic similarities with bininorganic dinuclear sites appear significant

Atherosclerosis prevention by a Fucus vesiculosus extract (HealseaTM)

Atherosclerosis is a multifactorial disease that can be modulated by polyphenols. Fucus vesiculosus is one of the species of brown algae which is rich in phlorotannins, varying its content according to the season, the period of harvest, the geographical origin, the level of irradiation and the stress inflicted by environmental and salinity. We designed an innovative Fucus vesiculosus extract standardized in total polyphenols (HealseaTM) and we tested its effects on vitamin C plasma levels in humans and performed animal studies to check the activity of this extract in the cardiovascular prevention field, especially atherosclerosis

Toxicity and antioxidant activity in vitro and in vivo of two Fucus vesiculosus extracts

The consumption of seaweeds has increased in recent years. However, their adverse and beneficial effects have scarcely been studied. Two extracts from the brown seaweed Fucus vesiculosus containing 28.8% polyphenols or 18% polyphenols plus 0.0012% fucoxanthin have been obtained and studied to determine their toxicity in mice and rats and also their antioxidant activity. Both extracts were shown to lack any relevant toxic effects in an acute toxicity test following a 4 week daily treatment in rats. The extracts exhibited antioxidant activity in noncellular systems and in activated RAW 264.7 macrophages, as well as in ex vivo assays in plasma and erythrocytes, after the 4 week treatment in rats. Our ex vivo results indicated that compounds from extract 2 may be more easily absorbed and that the antioxidants in their parent or metabolized form are more active. These findings support the view that the daily consumption of F. vesiculosus extract 2 (Healsea) would have potential benefits to humans