Free radical biology & medicine最新文献

{"title":"Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation.","authors":"Hinako Eto,&nbsp;Fuminori Hyodo,&nbsp;Nutavutt Kosem,&nbsp;Ryoma Kobayashi,&nbsp;Keiji Yasukawa,&nbsp;Motonao Nakao,&nbsp;Mamoru Kiniwa,&nbsp;Hideo Utsumi","doi":"10.1016/j.freeradbiomed.2015.10.418","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2015.10.418","url":null,"abstract":"<p><p>Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation. Female C57/BL6 mice received injections of 0.5% bupivacaine into their gastrocnemius muscles. Plasma biomarkers, myeloperoxidase activity, and histological sections were assessed at 4 and 24h after bupivacaine injection to measure the inflammatory response. In vivo DNP-MRI was performed with the nitroxyl radicals carbamoyl-PROXYL (cell permeable) and carboxy-PROXYL (cell impermeable) as molecular imaging probes at 4 and 24h after bupivacaine administration. The images obtained after carbamoyl-PROXYL administration were confirmed with the results of L-band EPR spectroscopy. The plasma biomarkers, myeloperoxidase activity, and histological findings indicated that bupivacaine injection caused acute muscle damage and inflammation. DNP-MRI images of mice treated with carbamoyl-PROXYL or carboxy-PROXYL at 4 and 24h after bupivacaine injection showed similar increases in image intensity and decay rate was significantly increased at 24h. In addition, reduction rates in individual mice at 4h and 24h showed faster trends with bupivacaine injection than in their contralateral sides by image-based analysis. These findings indicate that in vivo DNP-MRI with nitroxyl radicals can non-invasively detect changes in the focal redox status of muscle resulting from locally-induced inflammation. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1097-104"},"PeriodicalIF":7.4,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2015.10.418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34290761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer therapeutic potential of Mn porphyrin/ascorbate system.","authors":"Artak Tovmasyan,&nbsp;Romulo S Sampaio,&nbsp;Mary-Keara Boss,&nbsp;Jacqueline C Bueno-Janice,&nbsp;Bader H Bader,&nbsp;Milini Thomas,&nbsp;Julio S Reboucas,&nbsp;Michael Orr,&nbsp;Joshua D Chandler,&nbsp;Young-Mi Go,&nbsp;Dean P Jones,&nbsp;Talaignair N Venkatraman,&nbsp;Sinisa Haberle,&nbsp;Natalia Kyui,&nbsp;Christopher D Lascola,&nbsp;Mark W Dewhirst,&nbsp;Ivan Spasojevic,&nbsp;Ludmil Benov,&nbsp;Ines Batinic-Haberle","doi":"10.1016/j.freeradbiomed.2015.10.416","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2015.10.416","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Ascorbate (Asc) as a single agent suppressed growth of several tumor cell lines in a mouse model. It has been tested in a Phase I Clinical Trial on pancreatic cancer patients where it exhibited no toxicity to normal tissue yet was of only marginal efficacy. The mechanism of its anticancer effect was attributed to the production of tumoricidal hydrogen peroxide (H2O2) during ascorbate oxidation catalyzed by endogenous metalloproteins. The amount of H2O2 could be maximized with exogenous catalyst that has optimized properties for such function and is localized within tumor. Herein we studied 14 Mn porphyrins (MnPs) which differ vastly with regards to their redox properties, charge, size/bulkiness and lipophilicity. Such properties affect the in vitro and in vivo ability of MnPs (i) to catalyze ascorbate oxidation resulting in the production of H2O2; (ii) to subsequently employ H2O2 in the catalysis of signaling proteins oxidations affecting cellular survival pathways; and (iii) to accumulate at site(s) of interest. The metal-centered reduction potential of MnPs studied, E1/2 of Mn(III)P/Mn(II)P redox couple, ranged from -200 to +350 mV vs NHE. Anionic and cationic, hydrophilic and lipophilic as well as short- and long-chained and bulky compounds were explored. Their ability to catalyze ascorbate oxidation, and in turn cytotoxic H2O2 production, was explored via spectrophotometric and electrochemical means. Bell-shape structure-activity relationship (SAR) was found between the initial rate for the catalysis of ascorbate oxidation, vo(Asc)ox and E1/2, identifying cationic Mn(III) N-substituted pyridylporphyrins with E1/2&gt;0 mV vs NHE as efficient catalysts for ascorbate oxidation. The anticancer potential of MnPs/Asc system was subsequently tested in cellular (human MCF-7, MDA-MB-231 and mouse 4T1) and animal models of breast cancer. At the concentrations where ascorbate (1mM) and MnPs (1 or 5 µM) alone did not trigger any alteration in cell viability, combined treatment suppressed cell viability up to 95%. No toxicity was observed with normal human breast epithelial HBL-100 cells. Bell-shape relationship, essentially identical to vo(Asc)oxvs E1/2, was also demonstrated between MnP/Asc-controlled cytotoxicity and E1/2-controlled vo(Asc)ox. Magnetic resonance imaging studies were conducted to explore the impact of ascorbate on T1-relaxivity. The impact of MnP/Asc on intracellular thiols and on GSH/GSSG and Cys/CySS ratios in 4T1 cells was assessed and cellular reduction potentials were calculated. The data indicate a significant increase in cellular oxidative stress induced by MnP/Asc. Based on vo(Asc)oxvs E1/2 relationships and cellular toxicity, MnTE-2-PyP(5+) was identified as the best catalyst among MnPs studied. Asc and MnTE-2-PyP(5+) were thus tested in a 4T1 mammary mouse flank tumor model. The combination of ascorbate (4 g/kg) and MnTE-2-PyP(5+) (0.2mg/kg) showed significant suppression of tumor growth relative to either MnTE-2-PyP(5+) or","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1231-47"},"PeriodicalIF":7.4,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2015.10.416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34180177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting iron-mediated retinal degeneration by local delivery of transferrin.","authors":"Emilie Picard,&nbsp;Quentin Le Rouzic,&nbsp;Antonin Oudar,&nbsp;Marianne Berdugo,&nbsp;Mohamed El Sanharawi,&nbsp;Charlotte Andrieu-Soler,&nbsp;Marie-Christine Naud,&nbsp;Laurent Jonet,&nbsp;Chloé Latour,&nbsp;Christophe Klein,&nbsp;Stéphane Galiacy,&nbsp;François Malecaze,&nbsp;Hélène Coppin,&nbsp;Marie-Paule Roth,&nbsp;Jean-Claude Jeanny,&nbsp;Yves Courtois,&nbsp;Francine Behar-Cohen","doi":"10.1016/j.freeradbiomed.2015.08.018","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2015.08.018","url":null,"abstract":"<p><p>Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1105-21"},"PeriodicalIF":7.4,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2015.08.018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34143404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.","authors":"Adriana Covarrubias-Pinto,&nbsp;Pablo Moll,&nbsp;Macarena Solís-Maldonado,&nbsp;Aníbal I Acuña,&nbsp;Andrea Riveros,&nbsp;María Paz Miró,&nbsp;Eduardo Papic,&nbsp;Felipe A Beltrán,&nbsp;Carlos Cepeda,&nbsp;Ilona I Concha,&nbsp;Sebastián Brauchi,&nbsp;Maite A Castro","doi":"10.1016/j.freeradbiomed.2015.09.024","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2015.09.024","url":null,"abstract":"<p><p>Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1085-96"},"PeriodicalIF":7.4,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2015.09.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34078010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: \"Mitochondrial targeting of α-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy\" [Free Radic Biol Med. 50 (2011) 1546-1555].","authors":"Lan-Feng Dong,&nbsp;Victoria J A Jameson,&nbsp;David Tilly,&nbsp;Lubomir Prochazka,&nbsp;Jakub Rohlena,&nbsp;Karel Valis,&nbsp;Jaroslav Truksa,&nbsp;Renata Zobalova,&nbsp;Elahe Mahdavian,&nbsp;Katarina Kluckova,&nbsp;Marina Stantic,&nbsp;Jan Stursa,&nbsp;Ruth Freeman,&nbsp;Paul K Witting,&nbsp;Erik Norberg,&nbsp;Jacob Goodwin,&nbsp;Brian A Salvatore,&nbsp;Jana Novotna,&nbsp;Jaroslav Turanek,&nbsp;Miroslav Ledvina,&nbsp;Pavel Hozak,&nbsp;Boris Zhivotovsky,&nbsp;Mark J Coster,&nbsp;Stephen J Ralph,&nbsp;Robin A J Smith,&nbsp;Jiri Neuzil","doi":"10.1016/j.freeradbiomed.2013.08.164","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.08.164","url":null,"abstract":"","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"895-896"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.08.164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36464624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate measurement of nitrate, nitrite, and S-nitrosothiols in biological samples by mass spectrometry.","authors":"Dimitrios Tsikas,&nbsp;Anke Böhmer,&nbsp;Anja Mitschke,&nbsp;Pedro Araujo","doi":"10.1016/j.freeradbiomed.2013.07.010","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.07.010","url":null,"abstract":"","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"301-304"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.07.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31590854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung.","authors":"Robert D Bongard,&nbsp;Ke Yan,&nbsp;Raymond G Hoffmann,&nbsp;Said H Audi,&nbsp;Xiao Zhang,&nbsp;Brian J Lindemer,&nbsp;Mary I Townsley,&nbsp;Marilyn P Merker","doi":"10.1016/j.freeradbiomed.2013.07.040","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.07.040","url":null,"abstract":"<p><p>Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1455-1463"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.07.040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31629126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome alteration in oxidative stress-sensitive methionine sulfoxide reductase-silenced HEK293 cells.","authors":"Nicolas Ugarte,&nbsp;Romain Ladouce,&nbsp;Sabrina Radjei,&nbsp;Monique Gareil,&nbsp;Bertrand Friguet,&nbsp;Isabelle Petropoulos","doi":"10.1016/j.freeradbiomed.2013.08.008","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.08.008","url":null,"abstract":"<p><p>Methionine sulfoxide reductases (Msr's) are key enzymes proficient in catalyzing the reduction of oxidized methionines. This reductive trait is essential to maintaining cellular redox homeostasis from bacteria to mammals and is also regarded as a potential mechanism to regulate protein activities and signaling pathways, considering the inactivating effects that can be induced by methionine oxidation. In this study, we have generated stable human embryonic kidney HEK293 clones with an altered Msr system by silencing the expression of the main Msr elements-MsrA, MsrB1, or MsrB2. The isolated clones--the single mutants MsrA, MsrB1, and MsrB2 and double mutant MsrA/B1-show a reduced Msr activity and an exacerbated sensitivity toward oxidative stress. A two-dimensional difference in-gel electrophoresis analysis was performed on the Msr-silenced cells grown under basal conditions or submitted to oxidative stress. This proteomic analysis revealed that the disruption of the Msr system mainly affects proteins with redox, cytoskeletal or protein synthesis, and maintenance roles. Interestingly, most of the proteins found altered in the Msr mutants were also identified as potential Msr substrates and have been associated with redox or aging processes in previous studies. This study, through an extensive analysis of Msr-inhibited mutants, offers valuable input on the cellular network of a crucial maintenance system such as methionine sulfoxide reductases.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1023-1036"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.08.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31693139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-tocopherol attenuates moderate but not severe colitis and suppresses moderate colitis-promoted colon tumorigenesis in mice.","authors":"Qing Jiang,&nbsp;Ziying Jiang,&nbsp;Yava Jones Hall,&nbsp;Yumi Jang,&nbsp;Paul W Snyder,&nbsp;Carol Bain,&nbsp;Jianjie Huang,&nbsp;Amber Jannasch,&nbsp;Bruce Cooper,&nbsp;Yun Wang,&nbsp;Michelle Moreland","doi":"10.1016/j.freeradbiomed.2013.08.187","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.08.187","url":null,"abstract":"<p><p>Inflammation can promote colon cancer. Mechanistic studies indicate that γ-tocopherol (γT), a major form of vitamin E in diets, has anti-inflammatory and anticancer properties. Here we investigated the effectiveness of γT and a mixture of tocopherols against colitis and colitis-promoted colon tumorigenesis in male BALB/c mice. γT or mixed tocopherols (at 0.1% diet) did not show any effect on colon tumorigenesis induced by azoxymethane (AOM, 10mg/kg) with three cycles of dextran sodium sulfate (DSS at 1.5-2.5%). γT failed to exhibit protection of severe colitis caused by three cycles of DSS at 2.5%. In contrast, when AOM-initiated carcinogenesis was promoted by relatively mild colitis induced by one-cycle DSS (1.5%), γT, but not mixed tocopherols, suppressed total multiplicity of macroscopic adenomas (P=0.06) and large adenomatous polyps (>2mm(2), P<0.05) by 60 and 85%, respectively. γT also significantly decreased tumor multiplicity (>2mm(2)) induced by AOM with two cycles of 1.5% DSS even when dietary supplementation was started after AOM injection. Consistently, γT but not mixed tocopherols attenuated DSS (1.5%)-induced colon inflammation and damage as well as formation of atypical glandular hyperplasia. Mice supplemented with tocopherols had high fecal excretion of 13'-carboxychromanol, a long-chain vitamin E metabolite shown to have potent anti-inflammatory activities. Our study demonstrates that γT is able to alleviate moderate but not severe colitis and its promoted tumorigenesis, and indicates that inflammation severity should be considered in evaluating anticancer effectiveness of chemoprevention agents. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1069-1077"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.08.187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31715034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of superoxide dismutase isoenzymes and their genetic variants in progression of and higher susceptibility to vitiligo.","authors":"Naresh C Laddha,&nbsp;Mitesh Dwivedi,&nbsp;Amina R Gani,&nbsp;E M Shajil,&nbsp;Rasheedunnisa Begum","doi":"10.1016/j.freeradbiomed.2013.08.189","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.08.189","url":null,"abstract":"<p><p>Oxidative stress has been implicated as the initial triggering event in vitiligo pathogenesis leading to melanocyte destruction. Here, we report a significant increase in oxidative stress in vitiligo patients as evidenced by high lipid peroxidation levels suggesting an imbalance in the antioxidant enzyme system as reported in our previous studies. This study examined the role of the enzymatic antioxidant SOD, which converts the pro-oxidant superoxide into H2O2, in vitiligo pathogenesis. The activity of three isoforms of SOD, i.e., SOD1, SOD2, and SOD3, was significantly higher in vitiligo patients. To identify the underlying mechanism for the increase in activities of SOD isoforms, we explored the SOD1, SOD2, and SOD3 genes for their genetic variations and transcript levels. The SOD2 Thr58Ile (rs35289490) and Leu84Phe (rs11575993) polymorphisms were significantly associated with vitiligo patients, and the Val16Ala (rs4880) polymorphism was associated with active vitiligo patients. Interestingly, SOD2 activity was contributed by these polymorphisms along with its increase in transcript levels in patients. SOD3 activity was associated with the Arg213Gly (rs8192291) polymorphism. The SOD3 transcript levels were also increased in patients, which might contribute to the increased SOD3 activity. However, we could not establish the genotype-phenotype correlation for SOD1 as we could not detect any novel or reported SNPs in SOD1. In addition, both transcript and protein levels of SOD1 were unchanged between patients and controls, though SOD1 activity was increased in patients. Activities of SOD isoforms also correlated with progression of the disease as the activity was higher in active cases of vitiligo compared to stable cases. Here, we report that SOD2 and SOD3 polymorphisms may be genetic risk factors for susceptibility and progression of vitiligo and hence the genetic makeup of an individual may form a basis for the effective treatment of the disease. Overall, our results suggest that increased activity of SOD isoforms under the influence of genetic factors may lead to accumulation of H2O2 in cytoplasmic, mitochondrial, and extracellular compartments resulting in oxidative damage to the melanocytes. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1110-1125"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.08.189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31733885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}