Redox bases underlying the anti-tumor activity of garlic-contained organo-sulfur compounds: Implication in chemoprevention and chemotherapy

The beneficial effects of phytochemicals on human health have been extensively addressed. The majority of this outcome derives from their capability to function as antioxidants, thus the consumption of foods rich in these compounds is considered an advisable preventive therapy in slowing oxidative stress-mediated degenerative processes, such as those occurring during aging. Nevertheless, high concentrations of redox-active compounds could switch the antioxidant property to a pro-oxidant action leading to cell cycle arrest and death. This aspect place phytochemicals as promising therapeutics particularly for cancer prevention or treatment. Although their beneficial properties are known from ancient times, only during the recent years the molecular mechanisms underlying the anti-proliferative effects mediated by garlic-derived organo-sulfur compounds (OSC) are going to be clarified, with particular regard to what their pro-apoptotic features concerns. This chapter discusses the main findings that have contributed to the comprehension of OSC-mediated redox-dependent events governing growth arrest and apoptosis. Particularly, we report the mechanisms through which OSC have been suggested to generate reactive oxygen species and to modulate the redox state of specific reactive cysteines. Both processes will be argued as necessary events in inducing either irreversible damage to cellular macromolecules (e.g. DNA and cytoskeleton proteins), or waves of signaling finally resulting in the activation of the apoptotic program. In this perspective, the classes of proteins which have been indicated to represent the targets of OSC-mediated oxidative modifications, and to have a role in cellular redox response will be discussed

Magnetic Circular Dichroism of Cobalt-Copper and Zinc-Copper Bovine Superoxide Dismutase

Abstract The magnetic circular dichroism of the d-d transitions of Co(II) when substituted for Zn(II) in the Zn(II)-Cu(II) enzyme bovine superoxide dismutase enzyme is reported. Magnetic circular dichroism of the Co(II) chromophore in the Co(II)-Cu(II) enzyme is typical of tetrahedral Co(II) compounds. The magnetic circular dichroism band pattern is almost identical with the magnetic circular dichroism of the anion complexes of Co(II) carbonic anhydrase, implying similar coordination geometries in the two enzyme Co(II) complexes. The Cu(II) chromophore is only weakly induced by the magnetic field, with induced ellipticity an order of magnitude less than that of the Co(II) chromophore. Reduction of the Co(II)-Cu(II) protein causes minor, but significant, changes in the Co(II) site as measured by magnetic circular dichroism

Electron paramagnetic resonance studies of cobalt-copper bovine superoxide dismutase.

Abstract 1. EPR spectra of cobalt-copper bovine superoxide dismutase at liquid nitrogen and liquid helium temperature show that the two metal centers are magnetically coupled. The temperature dependence of the spectra indicates that this coupling arises from an exchange interaction. 2. The EPR spectrum of the Co(II) of the enzyme can only be seen after reduction of the Cu(II), at very low temperature. It is typical of tetrahedral coordination which is distorted in a particular way. The EPR parameters are g⊥ ≃ 4, g|| ≃ 2, D = 11.5 cm-1. No feature indicating interaction between the two Co(II) centers is observed. 3. Anions such as CN- and N3- do not affect the EPR spectrum of Co(II) significantly, but only modify the spectrum of Cu(II). It is concluded that the Co(II) site (and presumably the native Zn(II) site) can be described as distorted tetrahedral, strongly spin-coupled to the Cu(II) and therefore very near to it, and noninteracting with the other Co(II) site and with solvent molecules

Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials

Recent studies suggest that the toxicity of familial amyotrophic lateral sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective recruitment to mitochondria. Here we demonstrate that each of 12 different familial ALS-mutant SOD1s with widely differing biophysical properties are associated with mitochondria of motoneuronal cells to a much greater extent than wild-type SOD1, and that this effect may depend on the oxidation of Cys residues. We demonstrate further that mutant SOD1 proteins associated with the mitochondria tend to form cross-linked oligomers and that their presence causes a shift in the redox state of these organelles and results in impairment of respiratory complexes. The observation that such a diverse set of mutant SOD1 proteins behave so similarly in mitochondria of motoneuronal cells and so differently from wild-type SOD1 suggests that this behavior may explain the toxicity of ALS-mutant SOD1 proteins, which causes motor neurons to die

Regulatory and structural properties differentiating the chromosomal and the bacteriophage-associated Escherichia coli O157:H7 Cu, Zn Superoxide Dismutases

<p>Abstract</p> <p>Background</p> <p>Highly virulent enterohemorrhagic <it>Escherichia coli </it>O157:H7 strains possess three <it>sodC </it>genes encoding for periplasmic Cu, Zn superoxide dismutases: <it>sodC</it>, which is identical to the gene present in non-pathogenic <it>E. coli </it>strains, and <it>sodC</it>-F1 and <it>sodC</it>-F2, two nearly identical genes located within lambdoid prophage sequences. The significance of this apparent <it>sodC </it>redundancy in <it>E. coli </it>O157:H7 has not yet been investigated.</p> <p>Results</p> <p>We report that strains deleted of one or more <it>sodC </it>genes are less resistant than the wild type strain to a challenge with hydrogen peroxide, thus confirming their involvement in the bacterial antioxidant apparatus. To understand if the different <it>sodC </it>genes have truly overlapping functions, we have carried out a comparison of the functional, structural and regulatory properties of the various <it>E. coli </it>O157:H7 SodC enzymes. We have found that the chromosomal and prophagic <it>sodC </it>genes are differentially regulated <it>in vitro</it>. <it>sodC </it>is exclusively expressed in aerobic cultures grown to the stationary phase. In contrast, <it>sodC</it>-F1 and <it>sodC</it>-F2 are expressed also in the logarithmic phase and in anaerobic cultures. Moreover, the abundance of SodC-F1/SodC-F2 increases with respect to that of SodC in bacteria recovered from infected Caco-2 cells, suggesting higher expression/stability of SodC-F1/SodC-F2 in intracellular environments. This observation correlates with the properties of the proteins. In fact, monomeric SodC and dimeric SodC-F1/SodC-F2 are characterized by sharp differences in catalytic activity, metal affinity, protease resistance and stability.</p> <p>Conclusion</p> <p>Our data show that the chromosomal and bacteriophage-associated <it>E. coli </it>O157:H7 <it>sodC </it>genes have different regulatory properties and encode for proteins with distinct structural/functional features, suggesting that they likely play distinctive roles in bacterial protection from reactive oxygen species. In particular, dimeric SodC-F1 and SodC-F2 possess physico-chemical properties which make these enzymes more suitable than SodC to resist the harsh environmental conditions which are encountered by bacteria within the infected host.</p

A Novel Heme Protein, the Cu,Zn-Superoxide Dismutase from Haemophilus ducreyi

Haemophilus ducreyi, the causative agent of the genital ulcerative disease known as chancroid, is unable to synthesize heme, which it acquires from humans, its only known host. Here we provide evidence that the periplasmic Cu,Zn-superoxide dismutase from this organism is a heme-binding protein, unlike all the other known Cu,Zn-superoxide dismutases from bacterial and eukaryotic species. When the H. ducreyi enzyme was expressed in Escherichia coli cells grown in standard LB medium, it contained only limited amounts of heme covalently bound to the polypeptide but was able efficiently to bind exogenously added hemin. Resonance Raman and electronic spectra at neutral pH indicate that H. ducreyi Cu,Zn-superoxide dismutase contains a 6-coordinated low spin heme, with two histidines as the most likely axial ligands. By site-directed mutagenesis and analysis of a structural model of the enzyme, we identified as a putative axial ligand a histidine residue (His-64) that is present only in the H. ducreyi enzyme and that was located at the bottom of the dimer interface. The introduction of a histidine residue in the corresponding position of the Cu,Zn-superoxide dismutase from Haemophilus parainfluenzae was not sufficient to confer the ability to bind heme, indicating that other residues neighboring His-64 are involved in the formation of the heme-binding pocket. Our results suggest that periplasmic Cu,Zn-superoxide dismutase plays a role in heme metabolism of H. ducreyi and provide further evidence for the structural flexibility of bacterial enzymes of this class

COFLEX: FLEXIBLE BRACELET ANTI COVID-19 TO PROTECT CONSTRUCTION WORKERS

Abstract. To implement the protocol contrasting the diffusion of Covid-19, the employer is required, to ensure the safety and health of the worker at work, to adopt measures related to the control of body temperature (with respect for privacy), the minimum distance during work and all other activities such as breaks, canteen breaks, access to toilets, in addition to the adoption of specifically developed safety procedures, such as e.g. the use of man-down detection devices. In this context, the project aims to illustrate a system able of providing support in the safeguarding of workers' health on construction sites. This system, based on information received from sensors capable of identifying workers' positions (e.g., if less than 1m away) and their vital parameters (e.g., body temperature, gasped breathing), as well as moving objects inside the construction site area (e.g., to check if a worker is passing under a moving crane), will raise early alerts directly to the workers and/or to the central software, with respect for privacy, to immediately activate all the necessary measures to mitigate the risk. The system, based on the data communicated by the various sensors, will store and process them for the purpose of extracting useful information for risk management. The proposed system configured itself as a new product taking advantage from a high Technology Readiness Level maturated from the Smart Safety Belt already developed by some of the authors

Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells

Changes in intracellular redox status are crucial events that trigger downstream proliferation or death responses through activation of specific signaling pathways. Moreover, cell responses to oxidative challenge may depend on the pattern of redox-sensitive molecular factors. The stress-activated protein kinases c-Jun-N-terminal kinase (JNK) and p38 MAP kinase (p38(MAPK)) are implicated in different forms of apoptotic neuronal cell death. Here, we investigated the effects, on neuroblastoma cells, of the prooxidant molecule GSSG, which we previously demonstrated to be an efficient proapoptotic compound able to activate the p38(MAPK) death pathway in promonocytic cells. We found that neuroblastoma cells are not prone to GSSG-induced apoptosis, although the treatment slightly induced growth arrest through the accumulation of p53 and its downstream target gene, p21. However, GSSG treatment became cytotoxic when cells were previously depleted of intracellular GSH content. Under this condition, apoptosis was triggered by an increased production of superoxide that led to a specific activation of the JNK-dependent pathway. The involvement of superoxide and JNK was demonstrated by cell death inhibition in experiments carried out in the presence of Cu,Zn superoxide dismutase or with specific inhibitors of JNK activity. Our data give support to the studies that indicate preferential requirements for the involvement of stress-activated kinases in apoptotic neuronal cells. (c) 2005 Elsevier Inc. All rights reserved

The Domains of Human Nutrition: The Importance of Nutrition Education in Academia and Medical Schools

open28noHuman nutrition encompasses an extremely broad range of medical, social, commercial, and ethical domains and thus represents a wide, interdisciplinary scientific and cultural discipline. The high prevalence of both disease-related malnutrition and overweight/obesity represents an important risk factor for disease burden and mortality worldwide. It is the opinion of Federation of the Italian Nutrition Societies (FeSIN) that these two sides of the same coin, with their sociocultural background, are related to a low "nutritional culture" secondary, at least in part, to an insufficient academic training for health-care professionals (HCPs). Therefore, FeSIN created a study group, composed of delegates of all the federated societies and representing the different HCPs involved in human nutrition, with the aim of identifying and defining the domains of human nutrition in the attempt to more clearly define the cultural identity of human nutrition in an academically and professionally oriented perspective and to report the conclusions in a position paper. Three main domains of human nutrition, namely, basic nutrition, applied nutrition, and clinical nutrition, were identified. FeSIN has examined the areas of knowledge pertinent to human nutrition. Thirty-two items were identified, attributed to one or more of the three domains and ranked considering their diverse importance for academic training in the different domains of human nutrition. Finally, the study group proposed the attribution of the different areas of knowledge to the degree courses where training in human nutrition is deemed necessary (e.g., schools of medicine, biology, nursing, etc.). It is conceivable that, in the near future, a better integration of the professionals involved in the field of human nutrition will eventually occur based on the progressive consolidation of knowledge, competence, and skills in the different areas and domains of this discipline.openDonini, Lorenzo M; Leonardi, Francesco; Rondanelli, Mariangela; Banderali, Giuseppe; Battino, Maurizio; Bertoli, Enrico; Bordoni, Alessandra; Brighenti, Furio; Caccialanza, Riccardo; Cairella, Giulia; Caretto, Antonio; Cena, Hellas; Gambarara, Manuela; Gentile, Maria Gabriella; Giovannini, Marcello; Lucchin, Lucio; Migliaccio, Pietro; Nicastro, Francesco; Pasanisi, Fabrizio; Piretta, Luca; Radrizzani, Danilo; Roggi, Carla; Rotilio, Giuseppe; Scalfi, Luca; Vettor, Roberto; Vignati, Federico; Battistini, Nino C; Muscaritoli, MaurizioDonini, Lorenzo M; Leonardi, Francesco; Rondanelli, Mariangela; Banderali, Giuseppe; Battino, Maurizio; Bertoli, Enrico; Bordoni, Alessandra; Brighenti, Furio; Caccialanza, Riccardo; Cairella, Giulia; Caretto, Antonio; Cena, Hellas; Gambarara, Manuela; Gentile, Maria Gabriella; Giovannini, Marcello; Lucchin, Lucio; Migliaccio, Pietro; Nicastro, Francesco; Pasanisi, Fabrizio; Piretta, Luca; Radrizzani, Danilo; Roggi, Carla; Rotilio, Giuseppe; Scalfi, Luca; Vettor, Roberto; Vignati, Federico; Battistini, Nino C; Muscaritoli, Maurizi