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Free Radical Biology & Medicine

Yuan Ji, Fang Dai, Bo Zhou
Higher levels of copper, reduced glutathione (GSH) and reactive oxygen species (ROS) observed in cancer cells than in normal cells, favor the idea of developing copper ionophores as prooxidative anticancer agents (PAAs) to hit the altered redox homeostasis (redox Achilles heel) of cancer cells. In this work, we used salicylaldehyde isonicotinoyl hydrazone (SIH-1) as a basic scaffold to design Cu(II) ionophores with tunable chelation and release of Cu(II) by introducing electron-withdrawing nitro and electron-donating methoxyl groups in the para position to phenolic hydroxyl, or by blocking the phenolic hydroxyl site using methyl...
September 18, 2018: Free Radical Biology & Medicine
Panagiotis Lepetsos, Kostas A Papavassiliou, Athanasios G Papavassiliou
Human cells have to deal with the constant production of reactive oxygen species (ROS). Although ROS overproduction might be harmful to cell biology, there are plenty of data showing that moderate levels of ROS control gene expression by maintaining redox signaling. Osteoarthritis (OA) is the most common joint disorder with a multi-factorial etiology including overproduction of ROS. ROS overproduction in OA modifies intracellular signaling, chondrocyte life cycle, metabolism of cartilage matrix and contributes to synovial inflammation and dysfunction of the subchondral bone...
September 17, 2018: Free Radical Biology & Medicine
Marta Sanchez-Marinas, David Gimenez-Zaragoza, Edgar Martin-Ramos, Julia Llanes, José Cansado, Maria Jesús Pujol, Oriol Bachs, Rosa Aligue
Different studies have demonstrated multiple effects of arsenite on human physiology. However, there are many open questions concerning the mechanism of response to arsenite. Schizosaccharomyces pombe activates the Sty1 MAPK pathway as a common response to several stress conditions. The specificity of the response is due to the activation of different transcription factors and specific targets such the Cmk2 MAPKAP kinase. We have previously shown that Cmk2 is phosphorylated and activated by the MAPK Sty1 in response to oxidative stress...
September 17, 2018: Free Radical Biology & Medicine
W H Koppenol, R H Hider
A major form of toxicity arises from the ability of iron to redox cycle, that is, to accept an electron from a reducing compound and to pass it on to H2 O2 (the Fenton reaction). In order to do so, iron must be suitably complexed to avoid formation of Fe2 O3 . The ligands determine the electrode potential; this information should be known before experiments are carried out. Only one-electron transfer reactions are likely to be significant; thus two-electron potentials should not be used to determine whether an iron(III) complex can be reduced...
September 17, 2018: Free Radical Biology & Medicine
Ligia Akemi Kiyuna, Rudá Prestes E Albuquerque, Che-Hong Chen, Daria Mochly-Rosen, Julio Cesar Batista Ferreira
Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure...
September 15, 2018: Free Radical Biology & Medicine
Lisa Traeger, Inka Gallitz, Rohit Sekhri, Baumer Nicole Bäumer, Tanja Kuhlmann, Claudia Kemming, Michael Holtkamp, Muller Jennifer-Christin Müller, Uwe Karst, Francois Canonne-Hergaux, Martina U Muckenthaler, Donald B Bloch, Andrea Olschewski, Thomas B Bartnikas, Andrea U Steinbicker
The bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 are essential for expression of hepcidin, a key iron regulatory hormone. In mice, hepatocyte-specific Alk2 deficiency leads to moderate iron overload with periportal liver iron accumulation, while hepatocyte-specific Alk3 deficiency leads to severe iron overload with centrilobular liver iron accumulation and a more marked reduction of basal hepcidin levels. The objective of this study was to investigate whether the two receptors have additive roles in hepcidin regulation...
September 15, 2018: Free Radical Biology & Medicine
Rong Li, Xiaoqi Zhou, Dan Liu, Wei Feng
Dismutation of superoxide by superoxide dismutase (SOD) generates hydrogen peroxide, which may be reduced to hydroxyl radical. The generated H2 O2 during the catalysis can have an oxidative damage to SOD. Hydrogen peroxide decomposition by catalase (CAT) can help circumvent the problem. Mn-superoxide dismutase (herein referred to as SOD) and CAT are dimeric and tetrameric proteins, respectively. Herein, through intein-mediated in vivo subunit splicing, the C-terminus of the CAT subunit (CATS ) has been specifically ligated to the N-terminus of the SOD subunit (SODS ) with a peptide bond...
September 15, 2018: Free Radical Biology & Medicine
Yuyang Zhou, Min Lin, Jie Wang, Fan Chen, Feiyang Li, Wenge Chen, Longyu Han, Chiahung Wang, Jianming Chen, Jing-Wei Shao, Lee Jia
S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO donor with enhanced efficacy and reduced side effects. CapNO crystals are difficult to make due to its unstable S-NO bond. Here, we report a novel stable S-nitrosocaptopril monohydrate (CapNO·H2 O) that is stabilized by intermolecular five-membered structure, where one H of H2 O forms a hydrogen bond with O- of the stable resonance zwitterion Cap-S+ =N-O- , and the O in H2 O forms the dipole-dipole interaction with S+ through two unpaired electrons...
September 15, 2018: Free Radical Biology & Medicine
Ling Zhou, Yuetao Yi, Qing Yuan, Jing Zhang, Youjie Li, Pingyu Wang, Maolei Xu, Shuyang Xie
Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS in human NSCLC requires further study. In this study, VAOS exhibited effective inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse model. VAOS was further identified to induce NSCLC cell apoptosis through activating protein kinase B (AKT) to elevate intracellular reactive oxygen species (ROS) levels by increasing in oxygen consumption and impairing the ROS-scavenging system...
September 14, 2018: Free Radical Biology & Medicine
Ji Eun Choi, Seo-Hee Heo, Myung Ju Kim, Woo-Hyun Chung
A genetic analysis of synthetic lethal interactions in yeast revealed that the mutation of SOD1, encoding an antioxidant enzyme that scavenges superoxide anion radical, impaired the growth of a set of mutants defective in homologous recombination (HR) pathway. Hence, SOD1 inhibition has been proposed as a promising approach for the selective killing of HR-deficient cancer cells. However, we show that the deletion of RAD51 and SOD1 is not synthetic lethal but displays considerably slow growth and synergistic sensitivity to both reactive oxygen species (ROS)- and DNA double-strand break (DSB)-generating drugs in the budding yeast Saccharomyces cerevisiae...
September 14, 2018: Free Radical Biology & Medicine
Tobias M Seibt, Bettina Proneth, Marcus Conrad
Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. Dependence on NADPH/H+, polyunsaturated fatty acid metabolism, and the mevalonate and glutaminolysis metabolic pathways have been implicated in this novel form of regulated necrotic cell death. Genetic studies performed in cells and mice established the selenoenzyme glutathione peroxidase (GPX4) as the key regulator of this form of cell death. Besides these genetic models, the identification of a series of small molecule ferroptosis-specific inhibitors and inducers have not only helped in the delineation of the molecular underpinnings of ferroptosis but they might also prove highly beneficial when tipping the balance between cell death inhibition and induction in the context of degenerative diseases and cancer, respectively...
September 13, 2018: Free Radical Biology & Medicine
Alvaro Martinez Guimera, Daryl P Shanley, Carole J Proctor
The decline in the musculoskeletal system with age is driven at the cellular level by random molecular damage. Cells possess mechanisms to repair or remove damage and many of the pathways involved in this response are regulated by redox signals. However, with ageing there is an increase in oxidative stress which can lead to chronic inflammation and disruption of redox signalling pathways. The complexity of the processes involved has led to the use of computational modelling to help increase our understanding of the system, test hypotheses and make testable predictions...
September 13, 2018: Free Radical Biology & Medicine
James N Cobley, Giorgos K Sakellariou, Holger Husi, Brian McDonagh
Increased oxidative damage and disrupted redox signalling are consistently associated with age-related loss of skeletal muscle mass and function. Redox signalling can directly regulate biogenesis and degradation pathways and indirectly via activation of key transcription factors. Contracting skeletal muscle fibres endogenously generate free radicals (e.g. superoxide) and non-radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling can promote beneficial adaptive responses that are disrupted by age-related redox changes...
September 13, 2018: Free Radical Biology & Medicine
Hong-Na Mu, Quan Li, Jing-Yu Fan, Chun-Shui Pan, Yu-Ying Liu, Li Yan, Kai Sun, Bai-He Hu, Dan-Dan Huang, Xin-Rong Zhao, Xin Chang, Chuan-She Wang, Shu-Ya He, Ke He, Bao-Xue Yang, Jing-Yan Han
The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury, which represents a key issue in clinical transplantation determining early outcome and long-term graft survival. A solution is needed to deal with this insult. This study was undertaken to explore the effect of Caffeic acid (CA), a naturally occurring antioxidant, on I/R injury of grafted liver and the mechanisms involved. Male Sprague-Dawley rats underwent orthotopic liver transplantation (LT) in the absence or presence of CA administration...
September 12, 2018: Free Radical Biology & Medicine
Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato
BACKGROUND & AIMS: The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC). METHODS: Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n=38 HCC and 55 controls)...
September 12, 2018: Free Radical Biology & Medicine
Kazuhiro Iwai
Because of essentiality and toxicity of iron in our body, iron metabolism is tightly regulated in cells. In mammalian cells, iron regulatory protein 1 and 2 (IRP1 and IRP2) are the central regulators of cellular iron metabolism. IRPs regulate iron metabolism by interacting with the RNA stem-loop structures, iron-responsive elements (IREs), found on the transcripts encoding proteins involved in iron metabolism only in iron depleted condition. It is also well-known that the ubiquitin system plays central roles in cellular iron regulation because both IRPs having the IRE binding activity are recognized and ubiquitinated by the SCFFBXL5 ubiquitin ligase in condition of iron-replete...
September 12, 2018: Free Radical Biology & Medicine
D A Stoyanovsky, Y Y Tyurina, I Shrivastava, I Bahar, V A Tyurin, O Protchenko, S Jadhav, S B Bolevich, A V Kozlov, Y A Vladimirov, A A Shvedova, C C Philpott, H Bayir, V E Kagan
Duality of iron as an essential cofactor of many enzymatic metabolic processes and as a catalyst of poorly controlled redox-cycling reactions defines its possible biological beneficial and hazardous role in the body. In this review, we discuss these two "faces" of iron in a newly conceptualized program of regulated cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent form of regulated cell death driven by enhanced lipid peroxidation and insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4, GPX4) to eliminate hydroperoxy-lipids...
September 11, 2018: Free Radical Biology & Medicine
Jason P Eiserich, Sean P Ott, Tamara Kadir, Brian M Morrissey, Keri A Hayakawa, Michele A La Merrill, Carroll E Cross
RATIONALE: Cystic fibrosis (CF) patients are known to produce cyanide (CN- ) although challenges exist in determinations of total levels, the precise bioactive levels, and specificity of its production by CF microflora, especially P. aeruginosa. Our objective was to measure total CN- levels in CF sputa by a simple and novel technique in P. aeruginosa positive and negative adult patients, to review respiratory tract (RT) mechanisms for the production and degradation of CN- , and to interrogate sputa for post-transcriptal protein modification by CN- metabolites...
September 10, 2018: Free Radical Biology & Medicine
Lucilla Ribeiro Ávila, Clayson Moura Gomes, Pollyana Guimarães Oliveira, Rodrigo Saar Gomes, Marina Clare Vinaud, Miriam Leandro Dorta, Silvia Reni Bortolin Uliana, Fátima Ribeiro-Dias, Milton Adriano Pelli Oliveira
Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species (ROS). The aim of this study was to evaluate the ability of parasites obtained from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and amastigotes from LCL or ML isolates produced similar amounts of NO in culture. Promastigotes from ML isolates were more resistant to NO and H2 O2 than LCL parasites in a stationary phase, whereas amastigotes from LCL isolates were more resistant to NO...
September 7, 2018: Free Radical Biology & Medicine
Raquel Fernando, Cathleen Drescher, Kerstin Nowotny, Tilman Grune, José Pedro Castro
Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation...
September 5, 2018: Free Radical Biology & Medicine
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