Recombinant Human Voltage Dependent Anion Selective Channel Isoform 3 (hVDAC3) Forms Pores with a Very Small Conductance

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The Overexpression of Superoxide Dismutase 1 Restores Growth Defect in a Porin1-Less Yeast Strain and Improves Mitochondrial Metabolism

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Effects of Beta-Blockade on Exercise Performance at High Altitude

Summary Aims Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although β-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective β-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. Methods In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). Results HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO2, and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO2 was better preserved with nebivolol (–22.5%) than with carvedilol (–37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (–43.9 ± 11.9 beats/min) more than with nebivolol (–24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (–9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO2 at multivariate analysis (R= 0.62, P < 0.01). Conclusions Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects

A rapid and non-invasive method for authenticating the origin of pistachio samples by NIR spectroscopy and chemometrics

In this study, near-infrared spectroscopy coupled to chemometrics is used to build an analytical protocol to authenticate the origin of pistachio nuts (Pistacia vera L.), a high value-added food product. In particular, 483 samples from six different origins (Sicily, India, Iran, Syria, Turkey and U.S.A.) were analyzed by NIR spectroscopy. Spectra were recorded on half seeds cut longitudinally in reflectance mode. Spectral data were then processed by chemometrics to build classification models by SIMCA and PLS-DA. The discriminant approach resulted in classification accuracies higher than 90% for most of the classes. On the other hand, SIMCA built class-models with high sensitivity and specificities, the only exception being the two categories Turkey and Iran, whose heterogeneity resulted in a poorer specificity (anyway higher than 80%). In particular, the results obtained for the samples coming from Bronte (Sicily), the only PDO pistachio production in Europe 95.5% non-error rate in PLS-DA, 90% sensitivity and 97% specificity in SIMCA, as evaluated on the external test set are very promising from the viewpoint of the authentication of this product. In general, the results show that the coupling of NIR spectroscopy to chemometric classification techniques can be a valuable tool for tracing the origin of pistachio nuts, providing a reliable authentication in a rapid, relatively cheap and non-invasive way.Vitale, R.; Bevilacqua, M.; Bucci, R.; Magrì, A.; Magri, A.; Marini, F. (2013). A rapid and non-invasive method for authenticating the origin of pistachio samples by NIR spectroscopy and chemometrics. Chemometrics and Intelligent Laboratory Systems. 121:90-99. doi:10.1016/j.chemolab.2012.11.019S909912

Sex Differences in Repolarization Markers: Telemonitoring for Chronic Heart Failure Patients

Unlabelled: Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of the electrocardiogram (ECG) repolarization phase. Recently, some short period repolarization-dispersion parameters have been proposed as markers of acute decompensation and of mortality risk in CHF patients. Some important differences in repolarization between sexes are known, but their impact on ECG markers remains unstudied. The aim of this study was to evaluate possible differences between men and women in ECG repolarization markers for the telemonitoring of CHF patients. Method: 5 min ECG recordings were collected to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 215 decompensated CHF (age range: from 49 to 103 years). Thirty-day mortality and high levels of NT-pro BNP (&lt;75 percentile) were considered markers of decompensated CHF. Results: A total of 34 patients (16%) died during the 30-day follow-up, without differences between sexes. Women showed a more preserved ejection fraction and higher LDL and total cholesterol levels. Among female patients, implantable cardioverter devices, statins, and antiplatelet agents were less used. Data for Te mean showed increased values among deceased men and women compared to survival, but TeSD was shown to be the most reliable marker for CHF reacutization in both sexes. Conclusion: TeSD could be considered a risk factor for CHF worsening and complications for female and male patients, but different cut offs should be taken into account. (ClinicalTrials.gov number, NCT04127162.)

VDAC and SOD1: two major players in mitochondrial metabolism and in ALS

The Thesis work presented here has been devoted to two proteins, the Voltage-Dependent Anion Channel (VDAC) and the Superoxide Dismutase I (SOD1) and has been especially focused on the relationships between them in physiological or pathological conditions of the cell. VDAC is a pore-forming protein located in the outer mitochondrial membrane, where it is suspected to play a key role in metabolism regulation, as the interface between mitochondria and cytosol, and in apoptosis regulation. In the small family of VDAC proteins, composed of three isoforms in chordates, VDAC3 is the least known. Conversely from isoforms 1 and 2, its ability to form pores has been questioned. In this thesis, we present the first complete electrophysiological characterization of VDAC3, showing that this protein is able to forms smaller pores compared to VDAC1, under physiological condition of pH. Another point examined here has been the gating of VDAC1. This protein, in vitro, shows the important feature of gating the pore in dependence of high voltage applied. It is believed that the N-terminal domain has a crucial role in voltage-dependent gating and in the stabilization of the protein through its interaction with the pore-wall. By producing several mutants of VDAC1, in this work we have shown that the Voltage-dependence may be modulated in an asymmetrical way by modifying sequences or deleting £]-strands required for the interaction with N-terminal domain. The Superoxide Dismutase I (SOD1) is the most important antioxidant enzyme of all eukaryotic cells, since it inactivates the superoxide anion. Many recent evidences suggest that SOD1 is important for mitochondrial function, both in physiological and pathological conditions. SOD1 protects, among others, VDAC from oxidative stress, and may affect mitochondrial proteins expression levels. In addition, in the neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS), SOD1 mutants were reported to directly bind the cytosolic surface of mitochondria, using VDAC1 as docking site. To understand the relationships between VDAC and SOD1, in this work, we studied the influence of hSOD1 on mitochondria when it was overexpressed in a yeast strain devoid of yeast endogenous VDAC. Our results sturprisingly indicate that SOD1 may have a metabolic role and can support the mitochondrial recovery in the strain ´por1, heavily slowed down by the lack of porin1. Our results support the recent claim that SOD1 may act on the expression of other mitochondrial proteins. In addition, the characterization of the interaction between VDAC1 and two of the most diffused ALS-linked SOD1 mutants was also obtained and might be considered the molecular basis in understanding the mitochondrial involvement in ALS

VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis

Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies. Located in the outer mitochondrial membrane, VDAC forms channels that control the flux of ions and metabolites across the mitochondrion thus mediating the organelle's cross-talk with the rest of the cell. Furthermore, the interaction with both pro-apoptotic and anti-apoptotic factors makes VDAC a gatekeeper for mitochondria-mediated cell death and survival signaling pathways. Unfortunately, the lack of an evident druggability of this protein, since it has no defined binding or active sites, makes the quest for VDAC interacting molecules a difficult tale. Pharmacologically active molecules of different classes have been proposed to hit cancer and neurodegeneration. In this work, we provide an exhaustive and detailed survey of all the molecules, peptides, and microRNAs that exploit VDAC in the treatment of the two examined classes of pathologies. The mechanism of action and the potential or effectiveness of each compound are discussed

Special Issue “Mitochondrial Respiration in Physiology and Pathology”

Mitochondria are key organelles that regulate several functions essential for maintaining cellular homeostasis [...