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Guevara-Garcia M.,Biopharmaceutical and Chemical Group LABIOFAM | Valle L.G.-D.,Institute Pedro Kouri | Velasquez-Perez L.,Center For The Research And Rehabilitation Of Hereditary Ataxias Carlos nlay Cirah | Garcia-Rodriguez J.C.,National Center for Animal Breeding
Redox Report | Year: 2012

Spinocerebellar ataxia type 2 (SCA2) is a redox-sensitive neurodegenerative disease affecting the cerebellum, fibre connections in the cerebellum, the peripheral nervous system, and extracerebellar central pathways. Currently, Cuba has the highest reported global rate for this disease. The aim of this review article is to summarize and discuss the current knowledge about evidence of oxidative stress during SCA2. Recent reports have suggested that ataxin 2 and other related factors contribute to the redox imbalance in this disease. It is important to recognize and clarify the molecular mechanisms associated with the redox imbalance to consider ataxias innovative approaches to counteract oxidative stress-induced tissue damage, through alternative therapeutic or nutritional intervention in SCA2 and related diseases. © W.S. Maney &Son Ltd 2012. Source

Guevara-Garcia M.,Biopharmaceutical and Chemical Group LABIOFAM | Valle L.G.-D.,Institute Pedro Kouri | Martinez-Sanchez G.,Medinat Srl Clinic | Velasquez-Perez L.,Center For The Research And Rehabilitation Of Hereditary Ataxias Carlos nlay
Biomedicine and Aging Pathology | Year: 2012

Spinocerebellar ataxia 2 (SCA2) is a clinically, pathologically and genetically neurodegenerative disorder. The number of clinical assays in these patients is limited because, among other factors, a lack of biomarkers for the assessment of the main clinical and genetic features of the disease and the evaluation of therapeutic options. The aim of this study was to investigate an extensive array of redox status indexes: glutathione (GSH), malondialdehyde (MDA), peroxidation potential, superoxide dismutase (SOD), ferric reducing ability of plasma (FRAP), catalase (CAT), total hydroperoxide (TH) and advanced oxidation protein products (AOPP) by spectophotometric techniques in relation to electrophysiogical markers in-Cubans SCA2 patients compared to those of healthy aged-gender matched control. The Pearson correlation between progression markers and oxidative stress indexes were assessed too. Nineteen SCA2 patients' and 19 healthy subjects were recruited. Significant differences (P < 0.05) in PP, FRAP, GSH, SOD, AOPP and TH in SCA2 values were found relatively to the control group. The grade of oxidative reaction was evaluated as moderate to severe in almost markers for the studied group. Pearson significant correlation was found between PPLatMOS and FRAP-Lat. These results contribute both to the evidences that oxidative stress occurs during spinocerebellar ataxia type 2 and its useful for the integral management of patients. © 2012 Elsevier Masson SAS. All Rights Reserved. Source

Wada A.,Nagasaki University | Hasegawa M.,Nagahama Institute of Bio-Science and Technology | Wong P.-F.,University of Malaya | Shirai E.,Nagahama Institute of Bio-Science and Technology | And 7 more authors.
Glycobiology | Year: 2010

Gangliosides are target receptors for bacterial entry, yet those present in human milk exhibit a protective role against bacterial infection. Here, we show that treatment with ganglioside mixture at a concentration of 100 μg/mL resulted in significant inhibition of the vacuole formation activity of Helicobacter pylori vacuolating cytotoxin (VacA) in gastric epithelial cancer AZ-521 cells. All gangliosides (GM1, GM2, GM3, GD1a, GD1b, GD3 and GT1b) examined showed good neutralizing capacity against VacA. A pulldown assay was performed using lyso-GM1 coupled to Sepharose as the tagged polysaccharide polymer to capture VacA from H. pylori culture supernatant. GM1-VacA complexes were successfully precipitated, suggesting that GM1 binds directly to VacA. The hydrodynamic binding of lyso-GM1 and VacA measured by fluorescence correlation spectroscopy had a Kd value of 190 nM. VacA also bound to lyso-GM1 at pH 2 corresponding to the physiological pH of human stomach. Collectively, these results showed that direct binding of H. pylori VacA to free gangliosides neutralizes the toxin activity of VacA. These findings offer an alternative insight into the role of gangliosides in VacA toxicity and the pathogenesis of H. pylori. © The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org. Source

Wada A.,Nagasaki University | Wong P.-F.,University of Malaya | Hojo H.,Tokai University | Hasegawa M.,Nagahama Institute of Bio-Science and Technology | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Alarin is an alternative-splicing form of GALP (galanin-like peptide). It shares only 5 conserved amino acids at the N-terminal region with GALP which is involved in a diverse range of normal brain functions. This study seeks to investigate whether alarin has additional functions due to its differences from GALP. Here, we have shown using a radial diffusion assay that alarin but not GALP inhibited the growth of Escherichia coli (strain ML-35). The conserved N-terminal region, however, remained essential for the antimicrobial activity of alarin as truncated peptides showed reduced killing effect. Moreover, alarin inhibited the growth of E. coli in a similar potency as human cathelicidin LL-37, a well-studied antimicrobial peptide. Electron microscopy further showed that alarin induced bacterial membrane blebbing but unlike LL-37, it did not cause hemolysis of erythrocytes. In addition, alarin is only active against the gram-negative bacteria, E. coli but not the gram-positive bacteria, Staphylococcus aureus. Thus, these data suggest that alarin has potentials as an antimicrobial and should be considered for the development in human therapeutics. © 2013 Elsevier Inc. Source

Andriantsitohaina R.,French Institute of Health and Medical Research | Duluc L.,French Institute of Health and Medical Research | GarcIa-RodrIguez J.C.,National Center for Animal Breeding | Valle L.G.-D.,Institute Pedro Kouri | And 7 more authors.
Clinical Science | Year: 2012

Understanding the role of oxidative injury will allow for therapy with agents that scavenge ROS (reactive oxygen species) and antioxidants in the management of several diseases related to free radical damage. The majority of free radicals are generated by mitochondria as a consequence of the mitochondrial cycle, whereas free radical accumulation is limited by the action of a variety of antioxidant processes that reside in every cell. In the present review, we provide an overview of the mitochondrial generation of ROS and discuss the role of ROS in the regulation of endothelial and adipocyte function. Moreover, we also discuss recent findings on the role of ROS in sepsis, cerebral ataxia and stroke. These results provide avenues for the therapeutic potential of antioxidants in a variety of diseases. © The Authors Journal compilation © 2012 Biochemical Society. Source

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