Mitochondrial management of reactive oxygen species

Mitochondria in aerobic eukaryotic cells are both the site of energy production and the formation of harmful species, such as radicals and other reactive oxygen species, known as ROS. They contain an efficient antioxidant system, including low-molecular-mass molecules and enzymes that specialize in removing various types of ROS or repairing the oxidative damage of biological molecules. Under normal conditions, ROS production is low, and mitochondria, which are their primary target, are slightly damaged in a similar way to other cellular compartments, since the ROS released by the mitochondria into the cytosol are negligible. As the mitochondrial generation of ROS increases, they can deactivate components of the respiratory chain and enzymes of the Krebs cycle, and mitochondria release a high amount of ROS that damage cellular structures. More re-cently, the feature of the mitochondrial antioxidant system, which does not specifically deal with intramitochondrial ROS, was discovered. Indeed, the mitochondrial antioxidant system detoxifies exogenous ROS species at the expense of reducing the equivalents generated in mitochondria. Thus, mitochondria are also a sink of ROS. These observations highlight the importance of the mitochon-drial antioxidant system, which should be considered in our understanding of ROS-regulated pro-cesses. These processes include cell signaling and the progression of metabolic and neurodegenera-tive disease

Chlorella sorokiniana dietary supplementation increases antioxidant capacities and reduces ros release in mitochondria of hyperthyroid rat liver

The ability of aerobic organisms to cope with the attack of radicals and other reactive oxygen species improves by feeding on foods containing antioxidants. Microalgae contain many molecules showing in vitro antioxidant capacity, and their food consumption can protect cells from oxidative insults. We evaluated the capacity of dietary supplementation with 1% dried Chlorella sorokiniana strain 211/8k, an alga rich in glutathione, α-tocopherol, and carotenoids, to counteract an oxidative attack in vivo. We used the hyperthyroid rat as a model of oxidative stress, in which the increase in metabolic capacities is associated with an increase in the release of mitochondrial reactive oxygen species (ROS) and the susceptibility to oxidative insult. Chlorella sorokiniana supplementation prevents the increases in oxidative stress markers and basal oxygen consumption in hyperthyroid rat livers. It also mitigates the thyroid hormone-induced increase in maximal aerobic capacities, the mitochondrial ROS release, and the susceptibility to oxidative stress. Finally, alga influences the thyroid hormone-induced changes in the factors involved in mitochondrial biogenesis peroxisomal proliferator-activated receptor-γ coactivator (PGC1-1) and nuclear respiratory factor 2 (NRF-2). Our results suggest that Chlorella sorokiniana dietary supplementation has beneficial effects in counteracting oxidative stress and that it works primarily by preserving mitochondrial function. Thus, it can be useful in preventing dysfunctions in which mitochondrial oxidative damage and ROS production play a putative role

osteonecrosis of jaw onj impact of italian patients and role of italian physicians dentists and researchers in the growing evidence of a new disease

Purpose: Osteonecrosis of jaw (ONJ) is an uncommon but severe complication observed mostly in patients treated with bisphosphonates (BPs) for bone metastases, myeloma, osteoporosis (so called BRONJ, Bisphosphonate-Related Osteonecrosis of Jaw), but also with other drugs (bevacizumab, sunitinib, denosumab). The number of cases observed in Italy appears high in comparison with other countries and we present a review of several aspects of ONJ in Italy and the role of Italian health professionals and researchers on increasing knowledge and adequate reporting of ONJ phenomenon; Methods: Literature review about osteonecrosis of jaw (ONJ) with selection of Italian authors and publications, on year 2003-2011, by research on international electronic journal databases, Italian language journals, congress acta, web sources; Results: at October 2011, among 1272 papers published worldwide on ONJ issue, 128 (10%) were from Italian Authors; Conclusions: relevant articles by Italian groups were published about pathogenesis hypotheses, animal models, biology studies, risk factors, preventive measures, dental extraction protocols in BP-exposed patients, laser therapy, ozone therapy, surgical treatment. Experience of Italian patients suffering from ONJ, together with work of Italian dentists, physicians and researchers, appears of paramount importance in order to study ONJ and minimize a possible severe side-effect of efficacious medical treatments

COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome.

COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome. BACKGROUND: Mutations of the type IV collagen COL4A5 gene cause X-linked Alport syndrome (ATS). Mutations of COL4A3 and COL4A4 have been reported both in autosomal-recessive and autosomal-dominant ATS, as well as in benign familial hematuria (BFH). In the latter conditions, however, clinical features are less defined, few mutations have been reported, and other genes and non-genetic factors may be involved. METHODS: We analyzed 36 ATS patients for COL4A3 and COL4A4 mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Sporadic patients who had tested negative for COL4A5 mutations were included with typical cases of autosomal recessive ATS to secure a better definition of the phenotype spectrum. RESULTS: We identified seven previously undescribed COL4A3 mutations: in two genetic compounds and three heterozygotes, and one in COL4A4. In agreement with the literature, some of the mutations of compound heterozygotes were associated with microhematuria in healthy heterozygous relatives. The mutations of heterozygous patients are likely dominant, since no change was identified in the second allele even by sequencing, and they are predicted to result in shortened or abnormal chains with a possible dominant-negative effect. In addition, both genes showed rare variants of unclear pathogenicity, and common polymorphisms that are shared in part with other populations. CONCLUSIONS: This study extends the mutation spectrum of COL4A3 and COL4A4 genes, and suggests a possible relationship between production of abnormal COL IV chains and dominant expression of a continuous spectrum of phenotypes, from ATS to BFH

Nitrite stress and arginase activity in freshwater aquatic animals: similarities and differences between fish and shrimp

Adult specimens of the three species were acclimated at 27 C and a photoperiod of 14h: 10h L: D in separated tanks (biological filter+ dechlorinated tap water). They were individually treated with NaNO2 for 3h (A. nigrofasciata and C. multidentata, 2 mM and 1 mM, respectively), or 24h (D. rerio, 2 mM). Water samples were collected at intervals to determine the urea excretion; at the end of the treatment blood/haemolymph was collected, animals were euthanized and muscle tissue was dissected and frozen at-80 C. Animal procedures on fish were approved by the Institutional Animal Care and Use Committee (CESA) of the University of Naples Federico II, Naples, Italy. Blood samples were treated according to Dalla Via et al.(1994). Tissue samples were treated according to Dunn et al.(1986). Urea levels were measured with a diacetyl-monoxime method (Uliano et al. 2010). Urea excretion was expressed as mmol h-1 Kg-1. Nitrite was determined with the Griess method (Shechter et al., 1972)

Thyroid state affects H2O2 removal by rat heart mitochondria.

We investigated the effects of thyroid state on the mechanisms underlying rat heart mitochondrial capacity to remove H2O2 produced by an exogenous source. The removal rates were higher in the presence of respiratory substrates independently from thyroid state and were higher in hyperthyroid than in hypothyroid preparations. The thyroid state-linked changes in H2O2 removal rates, mirrored those in H2O2 release rates, showing that endogenous and exogenous H2O2 do not compete for the removing system. Mitochondrial content of coenzyme Q9 and Q10 was lower in hypothyroidism and higher in hyperthyroidism suggesting that the thyroid state-linked changes in the rates of H2O2 production are due to changes in the ubiquinone mitochondrial content. The rates of H2O2 removal in the presence of antioxidant enzyme inhibitors indicated that the contribution of each antioxidant is dependent on the thyroid state. This was supported by enzymatic activity measurements. Pharmacological inhibition also showed that the overall percentage contribution of the enzymatic processes, as well as that of non-enzymatic processes, is not affected by thyroid state. Cytochrome levels, inferred by light emission measurements, and western blot determination of cytochrome c, were lower in hypothyroid and higher in hyperthyroid preparations supporting the idea that the levels of reducing compounds were modified in opposite way by the changes in thyroid state. Further support was obtained showing that the whole antioxidant capacity, which provides an evaluation of capacity of the systems, different from cytochromes, assigned to H2O2 scavenging, was lower in hyperthyroid than in hypothyroid state