Cyclic Voltammetry and Computational Chemistry Studies on the Evaluation of the Redox Behavior of Parabens and other Analogues

Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food industries. The alkyl chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partition coefficient and redox properties. The voltammetric and computational analyses were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. A strong correlation between chemical substituents inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8 V for methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinonoidic forms showed great dependence on the substituent pattern.

Cyclic voltammetry and computational chemistry studies on the evaluation of the redox behavior of parabens and other analogues

Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food industries. The alkyl chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partition coefficient and redox properties. The voltammetric and computational analyses were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. A strong correlation between chemical substituents inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8 V for methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinonoidic forms showed great dependence on the substituent pattern.

Electrochemically activated coordenative assembly of a triruthenium cluster metallopolymer

A general strategy for electrochemically induced assembly of coordination metallopolymers is demonstrated using the tritopic bridging [Ru-3(mu(3)-O)(CH3COO)(6)(pytpy)(3)](+) cluster complex, where pytpy is the 4'-(4-pyridyl)-2,2':6',2 ''-terpyridine ligand, and iron(III) ions. The concept of such an electrochemically induced coordinative assembly was proven exploring the large difference in the [Fe(pytpy)2 complex formation constants depending on the iron ion oxidation state. Much more stable bridging complexes are formed in the presence of Fe(II) in contrast to Fe(III) ions. The build-up of electrochemically active films on FTO electrodes was confirmed by the growth of the corresponding voltammetric peaks concomitantly with the rise of typical triruthenium cluster and [Fe(pytpy)(2)](2+) complex absorption bands. The metallopolymer was constituted by agglomerates of more or less fused tape like structures, exhibiting large voids and pinholes, as revealed by SEM and AFM images. The adhesion/deposition on FTO was improved by functionalizing the surface with TES-tpy and HOOC-tpy, which increased the surface coverage up to 80%, as estimated by impedance spectroscopy. (C) 2012 Elsevier Ltd. All rights reserved.

Habitat alteration and community-level effects of an invasive ecosystem engineer: a case study along the coast of NSW, Australia

We investigated the effects of the habitat-modifying green algae Caulerpa taxifolia on meiobenthic communities along the coast of New South Wales, Australia. Samples were taken from unvegetated sediments, sediments underneath the native seagrass Zostera capricorni, and sediments invaded by C. taxifolia at 3 sites along the coast. Meiofaunal responses to invasion varied in type and magnitude depending on the site, ranging from a slight increase to a substantial reduction in meiofauna and nematode abundances and diversity. The multivariate structure of meiofauna communities and nematode assemblages, in particular, differed significantly in sediments invaded by C. taxifolia when compared to native habitats, but the magnitude of this dissimilarity differed between the sites. These differential responses of meiofauna to C. taxifolia were explained by different sediment redox potentials. Sediments with low redox potential showed significantly lower fauna abundances, lower numbers of meiofaunal taxa and nematode species and more distinct assemblages. The response of meiofauna to C. taxifolia also depended on spatial scale. Whereas significant loss of benthic biodiversity was observed locally at one of the sites, at the larger scale C. taxifolia promoted an overall increase in nematode species richness by favouring species that were absent from the native environments. Finally, we suggest there might be some time-lags associated with the impacts of C. taxifolia and point to the importance of considering the time since invasion when evaluating the impact of invasive species.

Functional and structural studies of the disulfide isomerase DsbC from the plant pathogen Xylella fastidiosa reveals a redox-dependent oligomeric modulation in vitro

Xylella fastidiosa is a Gram-negative bacterium that grows as a biofilm inside the xylem vessels of susceptible plants and causes several economically relevant crop diseases. In the present study, we report the functional and low-resolution structural characterization of the X. fastidiosa disulfide isomerase DsbC (XfDsbC). DsbC is part of the disulfide bond reduction/isomerization pathway in the bacterial periplasm and plays an important role in oxidative protein folding. In the present study, we demonstrate the presence of XfDsbC during different stages of X. fastidiosa biofilm development. XfDsbC was not detected during X. fastidiosa planktonic growth; however, after administering a sublethal copper shock, we observed an overexpression of XfDsbC that also occurred during planktonic growth. These results suggest that X. fastidiosa can use XfDsbC in vivo under oxidative stress conditions similar to those induced by copper. In addition, using dynamic light scattering and small-angle X-ray scattering, we observed that the oligomeric state of XfDsbC in vitro may be dependent on the redox environment. Under reducing conditions, XfDsbC is present as a dimer, whereas a putative tetrameric form was observed under nonreducing conditions. Taken together, our findings demonstrate the overexpression of XfDsbC during biofilm formation and provide the first structural model of a bacterial disulfide isomerase in solution. Structured digital abstract XfDsbC and XfDsbC bind by x ray scattering (View Interaction: 1, 2) XfDsbC and XfDsbC bind by molecular sieving (View interaction) XfDsbC and XfDsbC bind by comigration in non denaturing gel electrophoresis (View interaction) XfDsbC and XfDsbC bind by cross-linking study (View Interaction: 1, 2) XfDsbC and XfDsbC bind by dynamic light scattering (View Interaction: 1, 2)

Redox Control of 20S Proteasome Gating

The proteasome is the primary contributor in intracellular proteolysis. Oxidized or unstructured proteins can be degraded via a ubiquitin-and ATP-independent process by the free 20S proteasome (20SPT). The mechanism by which these proteins enter the catalytic chamber is not understood thus far, although the 20SPT gating conformation is considered to be an important barrier to allowing proteins free entrance. We have previously shown that S-glutathiolation of the 20SPT is a post-translational modification affecting the proteasomal activities. Aims: The goal of this work was to investigate the mechanism that regulates 20SPT activity, which includes the identification of the Cys residues prone to S-glutathiolation. Results: Modulation of 20SPT activity by proteasome gating is at least partially due to the S-glutathiolation of specific Cys residues. The gate was open when the 20SPT was S-glutathiolated, whereas following treatment with high concentrations of dithiothreitol, the gate was closed. S-glutathiolated 20SPT was more effective at degrading both oxidized and partially unfolded proteins than its reduced form. Only 2 out of 28 Cys were observed to be S-glutathiolated in the proteasomal alpha 5 subunit of yeast cells grown to the stationary phase in glucose-containing medium. Innovation: We demonstrate a redox post-translational regulatory mechanism controlling 20SPT activity. Conclusion: S-glutathiolation is a post-translational modification that triggers gate opening and thereby activates the proteolytic activities of free 20SPT. This process appears to be an important regulatory mechanism to intensify the removal of oxidized or unstructured proteins in stressful situations by a process independent of ubiquitination and ATP consumption. Antioxid. Redox Signal. 16, 1183-1194.

Electrostatic potentials and polarization effects in proton-molecule interactions by means of multipoles from the quantum theory of atoms in molecules

Some atomic multipoles (charges, dipoles and quadrupoles) from the Quantum Theory of Atoms in Molecules (QTAIM) and CHELPG charges are used to investigate interactions between a proton and a molecule (F2, Cl2, BF, AlF, BeO, MgO, LiH, H2CO, NH3, PH3, BF3, and CO2). Calculations were done at the B3LYP/6-311G(3d,3p) level. The main aspect of this work is the investigation of polarization effects over electrostatic potentials and atomic multipoles along a medium to long range of interaction distances. Large electronic charge fluxes and polarization changes are induced by a proton mainly when this positive particle approaches the least electronegative atom of diatomic heteronuclear molecules. The search for simple equations to describe polarization on electrostatic potentials from QTAIM quantities resulted in linear relations with r-4 (r is the interaction distance) for many cases. Moreover, the contribution from atomic dipoles to these potentials is usually the most affected contribution by polarization what reinforces the need for these dipoles to a minimal description of purely electrostatic interactions. Finally, CHELPG charges provide a description of polarization effects on electrostatic potentials that is in disagreement with physical arguments for certain of these molecules. (c) 2012 Wiley Periodicals, Inc.

Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells

Several epidemiological and experimental studies has been reported that lutein (LT) presents antioxidant properties. Aim of the present study was to investigate the protective effects of LT against oxidative stress and DNA damage induced by cisplatin (cDDP) in a human derived liver cell line (HepG2). Cell viability and DNA-damage was monitored by MU and comet assays. Moreover, different biochemical parameters related to redox status (glutathione, cytochrome-c and intracellular ROS) were also evaluated. A clear DNA-damage was seen with cDDP (1.0 mu M) treatment. In combination with the carotenoid, reduction of DNA damage was observed after pre- and simultaneous treatment of the cells, but not when the carotenoid was added to the cells after the exposure to cDDP. Exposure of the cells to cDDP also caused significant changes of all biochemical parameters and in co-treatment of the cells with LT, the carotenoid reverted these alterations. The results indicate that cDDP induces pronounced oxidative stress in HepG2 cells that is related to DNA damage and that the supplementation with the antioxidant LT may protect these adverse effects caused by the exposure of the cells to platinum compound, which can be a good predict for chemoprevention. (C) 2011 Elsevier Ltd. All rights reserved.

Asymptotic integral kernel for ensembles of random normal matrices with radial potentials

The method of steepest descent is used to study the integral kernel of a family of normal random matrix ensembles with eigenvalue distribution P-N (z(1), ... , z(N)) = Z(N)(-1)e(-N)Sigma(N)(i=1) V-alpha(z(i)) Pi(1 <= i<j <= N) vertical bar z(i) - z(j)vertical bar(2), where V-alpha(z) = vertical bar z vertical bar(alpha), z epsilon C and alpha epsilon inverted left perpendicular0, infinity inverted right perpendicular. Asymptotic formulas with error estimate on sectors are obtained. A corollary of these expansions is a scaling limit for the n-point function in terms of the integral kernel for the classical Segal-Bargmann space. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3688293]

From otoacoustic emission to late auditory potentials P300: the inhibitory effect

This study verifies the effects of contralateral noise on otoacoustic emissions and auditory evoked potentials. Short, middle and late auditory evoked potentials as well as otoacoustic emissions with and without white noise were assessed. Twenty-five subjects, normal-hearing, both genders, aged 18 to 30 years, were tested. In general, latencies of the various auditory potentials were increased at noise conditions, whereas amplitudes were diminished at noise conditions for short, middle and late latency responses combined in the same subject. The amplitude of otoacoustic emission decreased significantly in the condition with contralateral noise in comparison to the condition without noise. Our results indicate that most subjects presented different responses between conditions (with and without noise) in all tests, thereby suggesting that the efferent system was acting at both caudal and rostral portions of the auditory system.

Endurance training stimulates growth and survival pathways and the redox balance in rat pancreatic islets

Calegari VC, Abrantes JL, Silveira LR, Paula FM, Costa JM Jr, Rafacho A, Velloso LA, Carneiro EM, Bosqueiro JR, Boschero AC, Zoppi CC. Endurance training stimulates growth and survival pathways and the redox balance in rat pancreatic islets. J Appl Physiol 112: 711-718, 2012. First published December 15, 2011; doi:10.1152/japplphysiol.00318.2011.-Endurance training has been shown to increase pancreatic beta-cell function and mass. However, whether exercise modulates beta-cell growth and survival pathways signaling is not completely understood. This study investigated the effects of exercise on growth and apoptotic markers levels in rat pancreatic islets. Male Wistar rats were randomly assigned to 8-wk endurance training or to a sedentary control group. After that, pancreatic islets were isolated; gene expression and the total content and phosphorylation of several proteins related to growth and apoptotic pathways as well as the main antioxidant enzymes were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Reactive oxygen species (ROS) production was measured by fluorescence. Endurance training increased the time to reach fatigue by 50%. Endurance training resulted in increased protein phosphorylation content of AKT (75%), AKT substrate (AS160; 100%), mTOR (60%), p70s6k (90%), and ERK1/2 (50%), compared with islets from control group. Catalase protein content was 50% higher, whereas ROS production was 49 and 77% lower in islets from trained rats under basal and stimulating glucose conditions, respectively. Bcl-2 mRNA and protein levels increased by 46 and 100%, respectively. Bax and cleaved caspase-3 protein contents were reduced by 25 and 50% in islets from trained rats, respectively. In conclusion, these results demonstrate that endurance training favors the beta-cell growth and survival by activating AKT and ERK1/2 pathways, enhancing antioxidant capacity, and reducing ROS production and apoptotic proteins content.

Ethanol induces vascular relaxation via redox-sensitive and nitric oxide-dependent pathways

We investigated the role of reactive oxygen species (ROS) and nitric oxide (NO) in ethanol-induced relaxation. Vascular reactivity experiments showed that ethanol (0.03-200 mmol/L) induced relaxation in endothelium-intact and denuded rat aortic rings isolated from male Wistar rats. Pre-incubation of intact or denuded rings with L-NAME (non selective NOS inhibitor, 100 mu mol/L), 7-nitroindazole (selective nNOS inhibitor, 100 mu mol/L), ODQ (selective inhibitor of guanylyl cyclase enzyme, I mu mol/L), glibenclamide (selective blocker of ATP-sensitive K+ channels, 3 mu mol/L) and 4-aminopyridine (selective blocker of voltage-dependent K+ channels, 4-AP, 1 mmol/L) reduced ethanol-induced relaxation. Similarly, tiron (superoxide anion (O-2(-)) scavenger, 1 mmol/L) and catalase (hydrogen peroxide (H2O2) scavenger, 300 U/mL) reduced ethanol-induced relaxation to a similar extent in both endothelium-intact and denuded rings. Finally, prodifen (non-selective cytochrome P450 enzymes inhibitor, 10 mu mol/L) and 4-methylpyrazole (selective alcohol dehydrogenase inhibitor, 10 mu mol/L) reduced ethanol-induced relaxation. In cultured aortic vascular smooth muscle cells (VSMCs), ethanol stimulated generation of NO, which was significantly inhibited by L-NAME. In endothelial cells, flow cytometry studies showed that ethanol increased cytosolic Ca2+ concentration ([Ca2+]c), O-2(-) and cytosolic NO concentration ([NO]c). Tiron inhibited ethanol-induced increase in [Ca-2]c and [NO]c. The major new finding of this work is that ethanol induces relaxation via redox-sensitive and NO-cGMP-dependent pathways through direct effects on ROS production and NO signaling. These findings identify putative molecular mechanisms whereby ethanol, at pharmacological concentrations, influences vascular reactivity. (C) 2011 Elsevier Inc. All rights reserved.

Endophytic and rhizospheric enterobacteria isolated from sugar cane have different potentials for producing plant growth-promoting substances

Background and aims Endophytic and rhizospheric environments differ in many respects, leading to the presence of different bacterial communities at each site. However, microorganisms such as enterobacteria can be found both within plants and in the surrounding soil. Bacteria must present differences in the traits that affect such environments in order to successfully colonise them. The present study compared the plant growth-promoting potential of diazotrophic enterobacteria isolated from the rhizosphere and from within surface-disinfected plants. Methods A total of 46 diazotrophic enterobacterial strains (21 rhizospheric and 25 putatively endophytic) belonging to the Klebsiella and Enterobacter genera, which are prevalent in sugar cane plantations, were isolated from the rhizosphere and from surface-disinfected plants. Their ability to synthesise amino acids using combined nitrogen obtained from nitrogen fixation, and their ability to synthesise indole-3-acetic acid (IAA) were determined by high performance liquid chromatography. Endogenous ethylene production by the bacteria was measured using gas chromatography, and biocontrol of phytopathogenic fungi was determined qualitatively using a dual culture technique. Results The putative endophytes released significantly higher amounts of amino acids than the rhizospheric bacteria, whilst the latter produced higher quantities of ethylene and were more actively antagonistic to fungi. Both types of bacteria released similar amounts of IAA. Conclusion Endophytic and rhizospheric bacteria differ in their capacity to release plant growth-promoting substances, which may be a reflection of their adaptations and an indication of their potential impact on their natural environment.

Analysis of the Organic Hydroperoxide Response of Chromobacterium violaceum Reveals That OhrR Is a Cys-Based Redox Sensor Regulated by Thioredoxin

Organic hydroperoxides are oxidants generated during bacterial-host interactions. Here, we demonstrate that the peroxidase OhrA and its negative regulator OhrR comprise a major pathway for sensing and detoxifying organic hydroperoxides in the opportunistic pathogen Chromobacterium violaceum. Initially, we found that an ohrA mutant was hypersensitive to organic hydroperoxides and that it displayed a low efficiency for decomposing these molecules. Expression of ohrA and ohrR was specifically induced by organic hydroperoxides. These genes were expressed as monocistronic transcripts and also as a bicistronic ohrR-ohrA mRNA, generating the abundantly detected ohrA mRNA and the barely detected ohrR transcript. The bicistronic transcript appears to be processed. OhrR repressed both the ohrA and ohrR genes by binding directly to inverted repeat sequences within their promoters in a redox-dependent manner. Site-directed mutagenesis of each of the four OhrR cysteine residues indicated that the conserved Cys21 is critical to organic hydroperoxide sensing, whereas Cys126 is required for disulfide bond formation. Taken together, these phenotypic, genetic and biochemical data indicate that the response of C. violaceum to organic hydroperoxides is mediated by OhrA and OhrR. Finally, we demonstrated that oxidized OhrR, inactivated by intermolecular disulfide bond formation, is specifically regenerated via thiol-disulfide exchange by thioredoxin (but not other thiol reducing agents such as glutaredoxin, glutathione and lipoamide), providing a physiological reducing system for this thiol-based redox switch.

Speech perception and cortical auditory evoked potentials in cochlear implant users with auditory neuropathy spectrum disorders

Objective: To characterize the PI component of long latency auditory evoked potentials (LLAEPs) in cochlear implant users with auditory neuropathy spectrum disorder (ANSD) and determine firstly whether they correlate with speech perception performance and secondly whether they correlate with other variables related to cochlear implant use. Methods: This study was conducted at the Center for Audiological Research at the University of Sao Paulo. The sample included 14 pediatric (4-11 years of age) cochlear implant users with ANSD, of both sexes, with profound prelingual hearing loss. Patients with hypoplasia or agenesis of the auditory nerve were excluded from the study. LLAEPs produced in response to speech stimuli were recorded using a Smart EP USB Jr. system. The subjects' speech perception was evaluated using tests 5 and 6 of the Glendonald Auditory Screening Procedure (GASP). Results: The P-1 component was detected in 12/14 (85.7%) children with ANSD. Latency of the P-1 component correlated with duration of sensorial hearing deprivation (*p = 0.007, r = 0.7278), but not with duration of cochlear implant use. An analysis of groups assigned according to GASP performance (k-means clustering) revealed that aspects of prior central auditory system development reflected in the P-1 component are related to behavioral auditory skills. Conclusions: In children with ANSD using cochlear implants, the P-1 component can serve as a marker of central auditory cortical development and a predictor of the implanted child's speech perception performance. (c) 2012 Elsevier Ireland Ltd. All rights reserved.