Redoxoma Newsletter #2 – February 2015

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February-April 2015

  • Editor's Page:
    It is exciting to realize that the Newsletter is establishing itself as a communication vehicle between the Redoxoma group and a now expanded array of colleagues...""

CONTENTS • • • • • • • • Number #2 • • • • February 2015
html://redoxomanewsletter.iq.usp.br

The Redoxoma Newsletter is a bulletin issued by RIDC (CEPID) Redoxoma.
RIDC (CEPID) is supported by FAPESP. Homepage hosted by University of São Paulo - São Paulo, SP, Brazil

Editor’s Page

Editorial

We are back after a longer while than we expected. As with redox processes themselves, this delay was caused by good and bad things. The bad ones were a recurrent problem with our server, which caused our Newsletter to repeatedly get out of access. Hopefully it will be stable from now on, just as we hope to happen with redox homeostasis. The good things were recurrent bouts of very very hard work for our Editor, as well as for our colleagues, as chairs and organizers of international meetings, editors, authors of original as well as review articles, assistants for our research agencies , etc in addition of course to the usual duties at our universities. Similar to redox processes, we hope

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Editorial

Duality. That is the word of order of this issue of our Newsletter. Dual roles of enzymes as anti or prooxidants, dual roles of autophagy to protect or kill cancer cells, dual roles of redox processes to signal physiological processes or to contribute to disease-promoting mechanisms, and so on. Duality is not surprising, as we see that all along nature. But it is confusing to the scientist, who for sure would love to classify processes as either beneficial or damaging, given the pattern-seeking way our minds are structured. Things become even more confusing in the redox biology/chemistry area, given the several extra levels at which a given process can bifurcate across the “light-or-dark”

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Editorial

It is exciting to realize that the Newsletter is establishing itself as a communication vehicle between the Redoxoma group and a now expanded array of colleagues from Brazil and abroad. Welcome to all of you.

Thanks to the work of many colleagues, we have very exciting contributions, which emanate from research supported by our CEPID-Fapesp. In this issue, we can walk through intriguing paths, starting really from the beginning – with redox threads to the origin of life! And we end in a bold way, with a short essay from an experienced academic clinician, on how he interprets our redox area – leading us to think over where we should at the end direct our efforts. In

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Editorial

I am very excited to present our second number of our Redoxoma Newsletter. You will soon notice why. First, we have grown bigger, indicating that this newsletter is already turning into a good vehicle for communicating ourselves around the science of redox processes. Second, we have exciting comments on scientific productions from our Redoxoma team, and I am glad to know we have even more in the pipeline. In addition, we bring selected highlights from the literature which are likely to be of interest to everyone. Remarkably, some of these were brought about by young investigators from our team. My special thanks to them: you are more

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Peroxide signaling through thiol switches: chemical and biological aspects.

by Luis E. S. Netto

It is now well accepted that oxidants and other redox intermediates are not only damaging compounds, but also act as signaling molecules. This is especially evident for hydrogen peroxide, whose generation and degradation are finely regulated through multiple enzymatic systems. Proteins whose activities are based on Cysteine (Cys) residues are frequently reported to be oxidized in various biological systems in conditions where hydrogen peroxide is also generated. As the most parsimonious hypothesis, these proteins are frequently assumed to be directly oxidized by hydrogen peroxide, although this is not always supported by chemical data.

For instance, Protein Tyrosine Phosphatases

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Superoxide and nitric oxide induced nitrosative processes may follow unusual and different dynamic behaviors

by José Carlos Toledo

Possibly, most pathophysiological processes involving the radicals nitric oxide (NO•) and superoxide (O₂•–) depend on their simultaneous production and their favorable co-reaction to produce peroxynitrite. Peroxynitrite is an oxidant itself but in the presence of carbon dioxide it gives origin to radical species such as carbonate anion (CO₃•–) and nitrogen dioxide (NO₂•) radicals, both capable of stimulating oxidative and nitrosative events that damage biomolecules. The interplay of NO• and O₂•– in biological environments is complex, though. Using a fluorescent probe molecule to

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Visible, not only UV, light may also damage your hair and skin

by Mauricio Baptista

On the recent years, we aimed to understand the effects of visible light on skin and hair. We showed that melanin is able to photosensitize the generation of singlet oxygen both in the UVA (355nm) and in the visible (532nm) with similar yields and that the photosensitization of melanin forming singlet oxygen is the main cause of damage in hairs under exposition to visible light [1]. These results also suggest the possible role of visible light in damaging human skin, similarly to the well accepted effect of UVA light. In order to understand the effects

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More Tequila, please…: Organic nitrogen acquisition in Agave tequilana from endophytic bacteria by oxidative nitrogen scavenging mechanism

by Paolo Di Mascio

Historically, it was thought that plants derived all nitrogen (N) nutrition from the inorganic forms of N, NO3– and NH4+. However, it is now known that the principal form of N entering soils that do not receive inorganic fertilizer is organic N derived from microbial breakdown of organic matter, including amino acids, di and tri-peptides, DNA and proteins. Plants form symbiotic associations with endophytic bacteria

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A novel oxidative pathway for human SOD1 aggregation is revealed and may contribute to ALS pathology

by Ohara Augusto

ALS (amyotrophic lateral sclerosis) is a fatal disease characterized by the degeneration of motor neurons, resulting in progressive muscle weakness, atrophy, paralysis and death. Most cases of ALS are sporadic but about 10% of the cases have a genetic basis.ALS-causing mutations have been identified in several genes, but the mutation of Cu,Zn superoxide dismutase gene (SOD1) is the most studied and responsible for about 20% of the familial cases. SOD1-linked ALS patients exhibit pathology and symptoms similar to those of sporadic ALS patients, leading to the hypothesis that both forms of the disease have a common pathogenic mechanism. This hypothesis led to many advances in

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A novel ubiquitin-related marker in oxidative stress response

by Marilene Demasi

Protein polyubiquitination was first described as a post-translational modification to direct proteins for degradation. The ubiquitin molecule is covalently bound to the target protein and the polyubiquitin chain is created by successive attachments of ubiquitin through its carboxy-terminal Glycine mainly to Lysine48 (K48) residues of previously conjugated ubiquitin. Proteins tagged with a K48-linked polyubiquitin chain are directed for degradation. However, distinct ubiquitin chains are built up through other Lysine residues from ubiquitin, resulting in distinct structural patterns of ubiquitin complexes, which in most cases are unrelated to target protein degradation.

The

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Redoxcope

Peroxide signaling through thiol switches: chemical and biological aspects.

by Luis E. S. Netto

It is now well accepted that oxidants and other redox intermediates are not only damaging compounds, but also act as signaling molecules. This is especially evident for hydrogen peroxide, whose generation and degradation are finely regulated through multiple enzymatic systems. Proteins whose activities are based on Cysteine (Cys) residues are frequently reported to be oxidized in various biological systems in conditions where hydrogen peroxide is also generated. As the most parsimonious hypothesis, these proteins are frequently assumed to be directly oxidized by hydrogen peroxide, although this is not always supported by chemical data.

For instance, Protein Tyrosine Phosphatases

Read More...

Redoxoma highlights

An 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

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

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

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

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?

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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Education Page

Education page

by Carmen Fernandez

The CEPID-Redoxoma group had significant participation during events promoted by Universidade de São Paulo (USP) at the end of 2014 – I Virada Científica; Semana Nacional de Ciência e Tecnologia e 31ª Semana da Química. A folder about the project CEPID-Redoxoma was distributed to students and public in general during these events (Figure 1).

I Virada Científica was created by USP with the goal of making the world of science and technology closer to the São Paulo society. The event lasted 24 hours, starting 8am on October 11, and included workshops, experiments, shows, games, lectures, films and planetarium sessions – much of it aimed at children. Admission

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The radical-free corner

A radical-free talk about the scientific career: 3 Ds that allow for an E

by Francisco Laurindo

Can professionalism be learned? Certainly, to some extent, but likely not in the way you learn Chemistry or Biology, for example. But you can – and you should – discuss it, in order to trigger further thoughts that can help to achieve personal improvement. This is the idea of this short essay, derived from lectures given at our annual retreats over the years. While written with the young student in mind, I think it fits other ages as well… It should not be read rationally, but emotionally, just like it was written.

A general feeling among scientists is that science is not for everyone and that the scientific career is unusual in many aspects. To a good extent

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Highlights

Succinate accumulates during ischemia forcing mitochondrial complex I to operate in reversal, while producing oxidant species during reperfusion

by José Carlos Toledo

Ischemia-reperfusion (IR) is a process where blood supply (thus oxygen supply) to an organ is interrupted and then restored. While reperfusion is essential for survival, it is accompanied by a burst of mitochondrial generation of redox species and intermediates such as superoxide and hydrogen peroxide. Such species associate with derived ischemic tissue injury, underling disorders such as heart attack and stroke [1]. Nonetheless, IR mitochondrial ROS production has been considered a nonspecific consequence of a dysfunctional interaction of mitochondrial redox

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Saving the planet by eating healthier food

by Ignacio Amigo*

It is well established that as countries develop, their inhabitants change their alimentary habits from complex carbohydrates and fiber to diets with a higher proportion of fats, saturated fats and sugars, a phenomenon that has been termed “nutrition transition”. The link between these new food habits and the deterioration of health is notorious and underlies the great interest that consumers have developed in the last years over “organic” and “macrobiotic” aliments. Less obvious, but probably as important, is the association between the alimentary habits and greenhouse gases emissions. When we think about climate change, we usually picture big factories releasing

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The new roles of cardiolipin in ROS-mediated signalling

by Alberto Lévano-Martinez

Cardiolipin, the signature phospholipid of mitochondria, has been extensively studied as this organelle’s main structural and regulatory lipid. It exerts influential roles in the catalytic activity of key components of the oxidative phosphorylation under physiological conditions. However, recents advances in mitochondrial physiology have uncovered roles of this phospholipid in pathophysiological situations such as apoptosis, or in Barth syndrome. Cardiolipin anchors cytochrome c to the outer face of the inner mitochondrial membrane, which favors the electron transfer to the terminal component of the respiratory chain (Complex IV). However, during oxidative

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News

Development of a PDT protocol that avoids amputations in the diabetic feet

by Mauricio da Silva Baptista

Photoinduced reactions can be used to treat diseases such as cancer or microbial infections in a process called Photodynamic therapy. There are several indications of PDT in the areas of dermatology, oncology, vascular, blood supplies, ophthalmology. In addition to performing research in basic science related with PDT, CEPID Redoxoma researchers work in partnership with physicians, participating on clinical studies that aim to prove the potential of PDT in clinical medicine as can be seen in article published in 2014 [1]. There are several characteristics

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