An unexpected antiinflammatory route involving Nox2 NADPH Oxidase and thioredoxin

Redoxoma Highlights | F. LaurindoAn unexpected antiinflammatory route involving Nox2 NADPH Oxidase and thioredoxin

Nox NADPH oxidases are major sources of signaling oxidants in a variety of cell types, while in phagocytes Nox2 is essential for microbial killing and host defense. Genetic mutations impairing the Nox2 complex in humans associate with chronic granulomatous disease, a severe immunodeficiency that courses, however, with a paradoxical proinflammatory state. Recent work involving a cooperation between 2 CEPIDs, the Center for Research in Inflammatory Diseases (Fernando Q. Cunha) and Redoxoma (Lucia R Lopes) helped shedding light onto this complex phenomenon [1]. The investigators showed that during Nox2 activation, there is

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Protein disulfide isomerase regulates blood vessel caliber in vascular disease

Redoxoma Highlights | F. LaurindoPDI regulates blood vessel caliber in vascular disease

While the intuitive idea is that the lumen of diseased blood vessels narrows due to the pathological growth of a migrating cell mass, similar to rust in an old pipe, actually the lumen of diseased vessels is strongly influenced by a phenomenon called vascular remodeling, the structural reorganization of whole-vessel circumference. Typically, remodeling is the sole determinant of vessel lumen due to blood flow changes, in which redox signaling processes play an important mediator role in association with NO biovailability. However, redox processes appear to mediate other forms of vascular remodeling as well, such as those associated with atherosclerosis-related processes. We showed previously

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Mitochondria and lysosomes: lords of life and death in cells?

by Mauricio da Silva Baptista

An important aim of our CEPID-Redoxoma is to develop diagnostic and therapeutic applications of redox processes. In this context, antioxidant therapies are at the frontline of our interests as a group. In parallel, however, a smaller but nonetheless significant group of strategies aim to explore prooxidant and stress-enhancing effects of distinct interventions, mainly to achieve selective toxicity towards damaged or tumor cells. The group of Prof. Mauricio S. Baptisata, from our CEPID-Redoxoma, has been exploring for more than a decade photo-induced compounds as a means to achieve such type of effects. Interestingly, this group recently provided a significant contribution

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The complex relationship between omega-3 fatty acids and neurodegenerative diseases

by Sayuri Miyamoto

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is well known by its health-promoting effects. Being highly abundant in the brain, DHA displays essential role in neurological and visual development in infants. In adults, the decline of DHA content in brain has been associated to cognitive impairment and the use of omega-3 supplements have been thought to exert neuroprotective effects. Indeed, some studies indicated that consuming DHA would be beneficial for the prevention of cognitive disorders such as Alzheimer’s disease [1]. However, a recent clinical study involving 4000 participants has

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Together for ever…: Cross-linking of proteins by a ditryptophan bond

Cross-linking of proteins by a ditryptophan bond

by Verônica Paviani

Oxidative modifications of proteins are extensively investigated because proteins are major targets of radicals and oxidants under physiological conditions [1]. The amino acid residues most susceptible to oxidation are the sulfur-containing residues cysteine and methionine and the aromatic residues histidine, phenylalanine, tyrosine and tryptophan. The oxidation of cysteine and methionine residues is reversible and protein-cysteine oxidation is emerging as a fundamental cell regulatory mechanism. In contrast, the oxidation of all other protein residues is irreversible, and may result in loss of protein

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Mitochondria can dictate your fate, especially if you’re a stem cell

Redoxoma Highlights | Mitochondria can dictate your fate, especially if you’re a stem cell  Maria F. Forni

by Maria F. Forni*

Known for over a century, mitochondria have become, during the last four decades, an important subject of research within several disciplines. This is mostly due to the fact that this organelle comprises the site of oxidative phosphorylation, the citric acid cycle, fatty acid oxidation, the urea cycle and the biosynthesis of iron-sulphur centres and haem. Moreover, mitochondria are an important redox-signaling node. Indeed, the bioenergetic status of a cell is dependent on the overall quality and relative abundance of the mitochondrial population it harbors. Recent evidence suggests that the control of mitochondrial mass and morphology occurs through the processes of fusion

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The hard path towards accurately measuring in vivo enzyme activity: the case of protein disulfide isomerase

by Denise C. Fernandes

Correct protein folding is a vital and extremely regulated cellular function. Disulfide bonds are essential determinants of the correctly folded protein structure. During the folding of nascent proteins into the endoplasmic reticulum (ER) lumen, essential enzymes promote disulfide bond insertion (oxidation) and their eventual repositioning (isomerization) when they are initially formed between wrong cysteines. These reactions are catalyzed by PDIs (protein disulfide isomerases), a family of enzymes that contains more than 20 members, from yeast to humans [1]. Thus, PDIs do not have one specific substrate, but rather a large variety of un/misfolded protein substrates.

Using

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Mitochondria-to-nucleus communication controls mitochondrial activity and stress resistance in yeast

Redoxoma Highlights | Mitochondria-to-nucleus communication controls mitochondrial activity and stress resistance in yeast by Fernanda M. Cunha

by Fernanda M. Cunha

Mitochondria are believed to be former free living bacteria that established a successful symbiotic relationship with eukaryotic cells in such a way that today, besides being crucial for the biosynthesis of intermediary metabolites, calcium homeostasis, coordination of apoptosis and ATP synthesis, most mitochondrial proteins are encoded by nuclear rather than mitochondrial DNA. In that scenario, communication pathways that relay signals from the nucleus to mitochondria as well as from mitochondria to the nucleus (the retrograde way) are mandatory to secure energetic and metabolic homeostasis. In yeast, the best characterized retrograde signaling pathway, activated whenever

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Yes, together we can…. A highly conserved histidine residue in 2-Cys peroxiredoxins acts as a pH sensor for oligomerization

by Luis E. S. Netto

Peroxiredoxin (Prx) enzymes are becoming more and more popular among other reasons due to their high reactivity towards hydroperoxides and to their abundance. As a consequence, Prxs are proposed as biological sensors of hydrogen peroxide. It is interesting to observe that since their beginnings (in the end of the 60’s), one feature that called attention was their ability to form high molecular weight species, visible by electron microscopy [1]. It was almost twenty years later that the thiol-dependent peroxidase activity of Prx enzymes was described.

Among Prx family of proteins, 2-Cys Prx enzymes (those belonging to the AhpC/Prx1 group) can adopt a wide array of quartenary

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Is cholesterol bad for mitochondria?

Cholesterol

by Sayuri Miyamoto

Cholesterol is an important component of cell membranes and plays essential structural and signaling roles. It is synthesized in the endoplasmic reticulum and distributed to other cell membranes/compartments through a tightly regulated trafficking system involving vesicular and non-vesicular processes [1]. Cholesterol distribution among intra-cellular membranes is not homogeneous. Mitochondria are cholesterol-poor organelles (less than 5 %). However, mitochondrial cholesterol is increased in cancer cell lines and treatment of these cells with statins (cholesterol lowering drugs) increases their susceptibility to chemotherapy [2].

How mitochondrial cholesterol could influence

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