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Free Radical Biology & Medicine

Rayudu Gopalakrishna, Usha Gundimeda, Sarah Zhou, Bui Helena, Arne Holmgren
The cancer-preventive mechanism of selenium should address the way low concentrations of selenometabolites react with cellular targets without being diffused from the sites of generation, the way selenium selectively kills tumor cells, and the intriguing U-shaped curve that is seen with dietary supplementation of selenium and cancer prevention. Protein kinase C (PKC), a receptor for tumor promoters, is well suited for this mechanism. Due to the catalytic redox cycle, low concentrations of methylselenol, a postulated active metabolite of selenium, react with the tumor-promoting lipid hydroperoxide bound to PKC to form methylseleninic acid (MSA), which selectively reacts with thiol residues present within the vicinity of the PKC catalytic domain to inactivate it...
May 15, 2018: Free Radical Biology & Medicine
Xiuchun Li, Pan He, Xiaoliang Wang, Shuning Zhang, Neil Devejian, Edward Bennett, Chuanxi Cai
Cardiac stem/progenitor cells (CPCs) have recently emerged as a potentially transformative regenerative medicine to repair the infarcted heart. However, the limited survival of donor cells is one of the major challenges for CPC therapy. Our recent research effort on preconditioning human CPCs (hCPCs) with cobalt protoporphyrin (CoPP) indicated that sulfiredoxin-1 (SRXN1) is upregulated upon preconditioning aldehyde dehydrogenase bright hCPCs (ALDHbr -hCPCs) with CoPP. Further studies demonstrated that overexpressing SRXN1 enhanced the survival capacity for ALDHbr -hCPCs...
May 14, 2018: Free Radical Biology & Medicine
Florencia Orrico, Matías N Möller, Adriana Cassina, Ana Denicola, Leonor Thomson
Red blood cells (RBC) are considered as a circulating sink of H2 O2 , but a significant debate remains over the role of the different intraerythocyte peroxidases. Herein we examined the kinetic of decomposition of exogenous H2 O2 by human RBC at different cell densities, using fluorescent and oxymetric methods, contrasting the results against a mathematical model. Fluorescent measurements as well as oxygen production experiments showed that catalase was responsible for most of the decomposition of H2 O2 at cell densities suitable for both experimental settings (0...
May 9, 2018: Free Radical Biology & Medicine
Lei Chen, Junqing Zhang, Changhong Li, Ziwei Wang, Jingjing Li, Dan Zhao, Suxia Wang, Hong Zhang, Youyuan Huang, Xiaohui Guo
Oxidative stress is the main inducer of β-cell damage, which underlies the pathogenesis of diabetes. Evidence suggests that glycine, a recognized antioxidant, may improve β-cell function; however, its mechanism in protecting diabetic β-cells against oxidative stress has not been directly investigated. Using a streptozotocin-induced diabetic rat model and INS-1 pancreatic β-cells, we evaluated whether glycine can attenuate diabetic β-cell damage induced by oxidative stress. In diabetic rats, glycine stimulated insulin secretion; enhanced plasma glutathione (GSH), catalase and superoxide dismutase levels; reduced plasma 8-hydroxy-2 deoxyguanosine and islet p22phox levels; and improved islet β-cell mitochondrial degeneration and insulin granule degranulation...
May 9, 2018: Free Radical Biology & Medicine
Hongyun Wang, Xiyue Shen, Guoxiong Tian, Xili Shi, Wei Huang, Yongguang Wu, Lei Sun, Can Peng, Shasha Liu, Ying Huang, Xiaoyu Chen, Fang Zhang, Yingjie Chen, Wenjun Ding, Zhongbing Lu
Previous studies have demonstrated that long-term exposure to fine particulate matter (PM2.5 ) increases the risk of respiratory and cardiovascular diseases. As a metabolic sensor, AMP-activated protein kinase (AMPK) is a promising target for cardiovascular disease. However, the impact of AMPK on the adverse health effects of PM2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2-/- mice to either airborne PM2.5 (mean daily concentration ~64µg/m3 ) or filtered air for 6 months through a whole-body exposure system...
May 9, 2018: Free Radical Biology & Medicine
Valentina Gandin, Prajakta Khalkar, Jeremy Braude, Aristi P Fernandes
Selenium(Se)-containing compounds have attracted a growing interest as anticancer agents over recent decades, with mounting reports demonstrating their high efficacy and selectivity against cancer cells. Typically, Se compounds exert their cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis. However, the precise intracellular targets, signaling pathways affected and mechanisms of cell death engaged following treatment vary with the chemical properties of the selenocompound and its metabolites, as well as the cancer model that is used...
May 7, 2018: Free Radical Biology & Medicine
Qing Dong, Yajun Wang, Shaohua Qi, Kexin Gai, Qun He, Ying Wang
In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway...
May 5, 2018: Free Radical Biology & Medicine
Francesca Giuntini, Federica Foglietta, Arianna M Marucco, Adriano Troia, Nikolai V Dezhkunov, Alessandro Pozzoli, Gianni Durando, Ivana Fenoglio, Loredana Serpe, Roberto Canaparo
Ultrasound is used to trigger the cytotoxicity of chemical compounds, known as sonosensitisers, in an approach called sonodynamic therapy (SDT), which is under investigation herein. The generation of reactive oxygen species (ROS) has been proposed as the main biological occurrence that leads to the cytotoxic effects, which are achieved via the synergistic action of two components: the energy-absorbing sonosensitiser and ultrasound (US), which are both harmless per se. Despite some promising results, a lack of investigation into the mechanisms behind US sonosensitiser-mediated ROS generation has prevented SDT from reaching its full potential...
May 5, 2018: Free Radical Biology & Medicine
Leiming Wu, Lu Gao, Dianhong Zhang, Rui Yao, Zhen Huang, Binbin Du, Zheng Wang, Lili Xiao, Pengcheng Li, Yapeng Li, Cui Liang, Yanzhou Zhang
RATIONALE: Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. OBJECTIVE: To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. METHODS AND RESULTS: C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart...
May 4, 2018: Free Radical Biology & Medicine
Frank Van Breusegem, Christine Foyer, Giovanni Mann
No abstract text is available yet for this article.
May 3, 2018: Free Radical Biology & Medicine
Wei Li, David Kennedy, Zhili Shao, Xi Wang, Andre Klaassen Kamdar, Malory Weber, Kayla Mislick, Kathryn Kiefer, Rommel Morales, Brendan Agatisa-Boyle, Diana M Shih, Srinivasa T Reddy, Christine S Moravec, W H Wilson Tang
BACKGROUND: Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. METHODS AND RESULTS: Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression...
May 2, 2018: Free Radical Biology & Medicine
Erica J Dashner-Titus, Joseph Hoover, Luo Li, Ji-Hyun Lee, Ruofei Du, Ke Jian Liu, Maret G Traber, Emily Ho, Johnnye Lewis, G Hudson Laurie
No abstract text is available yet for this article.
April 30, 2018: Free Radical Biology & Medicine
Joseph M Feduska, Hubert M Tse
Type 1 diabetes (T1D) is an autoimmune disease culminating in the destruction of insulin-producing pancreatic β-cells. While ultimately a T cell-mediated disease, macrophages play an indispensable role in disease initiation and progression. Infiltrating macrophages generate an inflammatory environment by releasing NADPH oxidase-derived superoxide and proinflammatory cytokines. The synthesis of reactive oxygen species (ROS) is acknowledged as putative factors contributing to autoimmunity and β-cell damage in T1D...
April 30, 2018: Free Radical Biology & Medicine
Chang Liao, Bradley A Carlson, Robert F Paulson, K Sandeep Prabhu
Selenium (Se) is incorporated as the 21st amino acid selenocysteine (Sec) into the growing polypeptide chain of proteins involved in redox gatekeeper functions. Erythropoiesis presents a particular problem to redox regulation as the presence of iron, heme, and unpaired globin chains lead to high levels of free radical-mediated oxidative stress, which are detrimental to erythroid development and can lead to anemia. Under homeostatic conditions, bone marrow erythropoiesis produces sufficient erythrocytes to maintain homeostasis...
April 30, 2018: Free Radical Biology & Medicine
Wei Zhuang, Ting Li, Caiji Wang, Xi Shi, Yalan Li, Shili Zhang, Zeqi Zhao, Hongyan Dong, Yuehua Qiao
Cytomegalovirus (CMV) is the leading cause of sensorineural hearing loss (SNHL) in children because of its damage to the cochlea and spiral ganglion cells. Therefore, it has become a top priority to devise new methods to effectively protect spiral ganglion cells from damage. Berberine (BBR) has gained attention for its vast beneficial biological effects through immunomodulation, and its anti-inflammatory and anti-apoptosis properties. However, the effect of BBR on spiral ganglion cells and molecular mechanisms are still unclear...
April 28, 2018: Free Radical Biology & Medicine
Jiwoon Na, Jisu Jung, Jeyoung Bang, Qiao Lu, Bradley A Carlson, Xiong Guo, Vadim N Gladyshev, Jinhong Kim, Dolph L Hatfield, Byeong Jae Lee
Selenophosphate synthetase (SEPHS) synthesizes selenophosphate, the active selenium donor, using ATP and selenide as substrates. SEPHS was initially identified and isolated from bacteria and has been characterized in many eukaryotes and archaea. Two SEPHS paralogues, SEPHS1 and SEPHS2, occur in various eukaryotes, while prokaryotes and archaea have only one form of SEPHS. Between the two isoforms in eukaryotes, only SEPHS2 shows catalytic activity during selenophosphate synthesis. Although SEPHS1 does not contain any significant selenophosphate synthesis activity, it has been reported to play an essential role in regulating cellular physiology...
April 28, 2018: Free Radical Biology & Medicine
Ji Won Park, Choon-Myung Lee, Joan S Cheng, Edward T Morgan
Nitric oxide (NO) is an essential signaling molecule in the body, regulating numerous biological processes. Beside its physiological roles, NO affects drug metabolism by modulating the activity and/or expression of cytochrome P450 enzymes. Previously, our lab showed that NO generation caused by inflammatory stimuli results in CYP2B6 degradation via the ubiquitin-proteasome pathway. In the current study, we tested the NO-mediated regulation of CYP2J2 that metabolizes arachidonic acids to bioactive epoxyeicosatrienoic acids, as well as therapeutic drugs such as astemizole and ebastine...
April 28, 2018: Free Radical Biology & Medicine
Qi Li, Mingyu Zhang, Lina Xuan, Yanli Liu, Chang Chen
Intimal hyperplasia is one of the major complications after stenting, but the underlying mechanisms remain unclear. Our previous study found that the dipeptidyl peptidase IV (DPP-4) inhibitor, Anagliptin, suppresses intimal hyperplasia after balloon injury. Here, we further investigated the effects of Anagliptin on endothelial cell (EC) migration after balloon injury. The results showed that Anagliptin administration significantly reduced intimal hyperplasia by stimulating the migration of endothelial cells, but had no effect on the medial area after balloon injury...
April 28, 2018: Free Radical Biology & Medicine
Noelia Fradejas-Villar
In its 200 years of history, selenium has been defined first as a toxic element and finally as a micronutrient. Selenium is incorporated into selenoproteins as selenocysteine (Sec), the 21st proteinogenic amino acid codified by a stop codon. Specific biosynthetic factors recode UGA stop codon as Sec. The significance of selenoproteins in human health is manifested through the identification of patients with inborn errors in selenoproteins or their biosynthetic factors. Selenoprotein N-related myopathy was the first disease identified due to mutations in a selenoprotein gene...
April 27, 2018: Free Radical Biology & Medicine
Qing Li, Jie Su, Shi-Jie Jin, Wei Wei, Xiao-Dong Cong, Xiao-Xue Li, Ming Xu
BACKGROUND: Insulin resistance in endothelial cells contributes to the development of cardiovascular disease in type 2 diabetes mellitus (T2DM). Therefore, there are great potential clinical implications in developing pharmacological interventions targeting endothelial insulin resistance. Our previous studies indicated that argirein which was developed by combining rhein with L-arginine by a hydrogen bond, could substantially relieved stress related exacerbation of cardiac failure and alleviated cardiac dysfunction in T2DM, which was associated with suppressing NADPH oxidase activity...
April 27, 2018: Free Radical Biology & Medicine
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