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Free Radical Biology & Medicine

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https://www.readbyqxmd.com/read/28712859/tyr42-phosphorylation-of-rhoa-gtpase-promotes-tumorigenesis-through-nuclear-factor-nf-%C3%AE%C2%BAb
#1
Jae-Gyu Kim, Kyoung-Chan Choi, Chang-Won Hong, Hwee-Seon Park, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Bong Park
Dysregulation of reactive oxygen species (ROS) levels is implicated in the pathogenesis of several diseases, including cancer. However, the molecular mechanisms of ROS in tumorigenesis have not been clearly elucidated. Hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide phosphorylated RhoA at Tyr42 via Src. P-Ty42 residue of RhoA was a binding site of Vav2, a guanine nucleotide exchange factor (GEF) that activates p-Tyr42 RhoA. P-Tyr42 RhoA then bound to IκB kinase γ (IKKγ), leading IKKβ activation...
July 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28711502/a-small-molecule-activator-of-sirt3-promotes-deacetylation-and-activation-of-manganese-superoxide-dismutase
#2
Jiaqi Lu, Hua Zhang, Xian Chen, Yong Zou, Jiasong Li, Li Wang, Minhao Wu, Jianye Zang, Yang Yu, Wei Zhuang, Qing Xia, Jiangyun Wang
The modulation of protein acetylation network is a promising strategy for life span extension and disease treatment.(1-2) A variety of small molecules have been developed to target deacetylases, but extremely few of these molecules are capable of activating the mitochondrial NAD-dependent deacetylase sirtuin-3 (SIRT3).(3-4) Manganese superoxide dismutase (MnSOD) is the major superoxide scavenger in mitochondria, whose activity is regulated by SIRT3-mediated deacetylation, particularly at the Lys68 site.(5) To investigate the influence of Lys68 acetylation on MnSOD activity, we produced a mutant MnSOD protein-bearing N-acetyllysine (AcK) at its Lys68 position through the genetic code expansion approach...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28709976/glutathione-peroxidase-4-catalyzed-reduction-of-lipid-hydroperoxides-in-membranes-the-polar-head-of-membrane-phospholipids-binds-the-enzyme-and-addresses-the-fatty-acid-hydroperoxide-group-toward-the-redox-center
#3
Giorgio Cozza, Monica Rossetto, Valentina Bosello-Travain, Matilde Maiorino, Antonella Roveri, Stefano Toppo, Mattia Zaccarin, Lucio Zennaro, Fulvio Ursini
GPx4 is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids. This reaction inhibits lipid peroxidation and accounts for enzyme's vital role. Here we investigated the interaction of GPx4 with membrane phospholipids. A cationic surface near the GPx4 catalytic center interacts with phospholipid polar heads. Accordingly, SPR analysis indicates cardiolipin as the phospholipid with maximal affinity to GPx4. Consistent with the electrostatic nature of the interaction, KCl increases the KD...
July 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28705658/disturbance-of-redox-homeostasis-in-down-syndrome-role-of-iron-dysmetabolism
#4
REVIEW
Eugenio Barone, Andrea Arena, Elizabeth Head, D Allan Butterfield, Marzia Perluigi
Down syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD). The neuropathology of DS has several common features with AD including alteration of redox homeostasis, mitochondrial deficits, and inflammation among others. Interestingly, some of the genes encoded by chromosome 21 are responsible of increased oxidative stress (OS) conditions that are further exacerbated by decreased antioxidant defense...
July 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28705657/role-of-glutathione-in-the-regulation-of-epigenetic-mechanisms-in-disease
#5
REVIEW
José Luis García-Giménez, Carlos Romá-Mateo, Gisselle Pérez-Machado, Lorena Peiró-Chova, Federico V Pallardó
Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function...
July 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28697922/gl-v9-induced-upregulation-and-mitochondrial-localization-of-nag-1-associates-with-ros-generation-and-cell-death-in-hepatocellular-carcinoma-cells
#6
Xiaobo Zhang, Yue Kang, Tongxin Huo, Ran Tao, Xiaoping Wang, Zhiyu Li, Qinglong Guo, Li Zhao
We have previously reported that a newly synthesized compound, GL-V9 could induce mitochondria-mediated apoptosis in HepG2 cells. However, the underlying mechanisms have not been fully understood yet. In current study, we further showed that GL-V9 exhibited significant inhibitory effect on growth of several hepatocellular carcinoma cell lines. Moreover, GL-V9-induced growth inhibition was coincident with the strong upregulation of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a TGFβ superfamily member, which has been linked with tumor suppression...
July 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28690198/punicalagin-a-ptp1b-inhibitor-induces-m2c-phenotype-polarization-via-up-regulation-of-ho-1-in-murine-macrophages
#7
Xiaolong Xu, Yuhong Guo, Jingxia Zhao, Shasha He, Yan Wang, Yan Lin, Ning Wang, Qingquan Liu
Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC50 value of 1.04μM. Results from NPOI further showed that the Kon and Koff of PUN-PTP1B complex were 3.38e2M(-1)s(-1) and 4.13e-3s(-1), respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation...
July 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28690197/high-fat-diet-induces-skeletal-muscle-oxidative-stress-in-a-fiber-type-dependent-manner-in-rats
#8
Ricardo A Pinho, Diane M Sepa-Kishi, George Bikopoulos, Michelle V Wu, Abinas Uthayakumar, Arta Mohasses, Meghan C Hughes, Christopher G R Perry, Rolando B Ceddia
This study investigated the effects of high-fat (HF) diet on parameters of oxidative stress among muscles with distinct fiber type composition and oxidative capacities. To accomplish that, male Wistar rats were fed either a low-fat standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus (EDL), and epitrochlearis muscles were collected and mitochondrial H2O2 (mtH2O2) emission, palmitate oxidation, and gene expression and antioxidant system were measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic muscles...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28690196/linking-arsenite-and-cadmium-generated-oxidative-stress-to-microsatellite-instability-in-vitro-and-in-vivo
#9
Chang-Lin Wu, Li-Yan Huang, Christina L Chang
Mismatch repair (MMR) corrects replicative errors and minimizes DNA damage that occurs frequently in microsatellites. MMR deficiency is manifested as microsatellite instability (MSI), which contributes to hypermutability and cancer pathogenesis. Genomic instability, including MSI and chromosomal instability, appears to be responsible for the carcinogenesis of arsenic and cadmium, common contaminants in our environment. However, few studies have addressed arsenic- or cadmium-induced MSI, especially its potential link with arsenic- or cadmium-generated oxidative stress, due to the lack of quantifiable MSI assays and cost-effective animal models...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28690195/low-molar-excess-of-4-oxo-2-nonenal-and-4-hydroxy-2-nonenal-promote-oligomerization-of-alpha-synuclein-through-different-pathways
#10
Leire Almandoz-Gil, Hedvig Welander, Elisabet Ihse, Payam Emami Khoonsari, Sravani Musunuri, Christofer Lendel, Jessica Sigvardson, Mikael Karlsson, Martin Ingelsson, Kim Kultima, Joakim Bergström
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal inclusions found in brains with Parkinson's disease and dementia with Lewy bodies. A body of evidence implicates oxidative stress in the pathogenesis of these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can induce alpha-synuclein oligomer formation. The objective of the study was to investigate the effect of these reactive aldehydes on alpha-synuclein at a lower molar excess (3:1) at both physiological (7...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28690194/examining-a-role-for-pkg-i%C3%AE-oxidation-in-the-pathogenesis-of-cardiovascular-dysfunction-during-diet-induced-obesity
#11
Olena Rudyk, Philip Eaton
BACKGROUND: Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#12
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28687409/ephb2-signaling-mediated-sirt3-expression-reduces-msc-senescence-by-maintaining-mitochondrial-ros-homeostasis
#13
Young Hyun Jung, Hyun Jik Lee, Jun Sung Kim, Sei-Jung Lee, Ho Jae Han
Disruption of mitochondrial reactive oxygen species (mtROS) homeostasis is a key factor inducing UCB-MSC senescence. Accordingly, preventing mtROS accumulation will help in suppressing the UCB-MSC senescence. In this study, we observed that the expressions of EphrinB2 and EphB2 were inversely regulated by UCB-MSC passage-dependent manner. EphB2 signaling induced mitochondrial translocation of Sirt3. The knockdown of SIRT3 inhibited the effect of EphB2 signaling in UCB-MSCs. Subsequently, EphrinB2-Fc induced the nuclear translocation of Nrf-2 via c-Src phosphorylation dependent manner, and Sirt3 expression was regulated by Nrf-2...
July 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28684161/vitamin-e-isoform-%C3%AE-tocotrienol-protects-against-emphysema-in-cigarette-smoke-induced-copd
#14
Hong Yong Peh, W S Daniel Tan, Tze Khee Chan, Chen Wei Pow, Paul S Foster, W S Fred Wong
Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months...
July 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28673614/ros-dependent-activation-of-rhoa-rho-kinase-in-pulmonary-artery-role-of-src-family-kinases-and-arhgef1
#15
Charles E MacKay, Yasin Shaifta, Vladimir V Snetkov, Asvi A Francois, Jeremy P T Ward, Greg A Knock
The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses were inhibited by antioxidants (ebselen, Tempol)...
July 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28673615/hcv-induced-oxidative-stress-by-inhibition-of-nrf2-triggers-autophagy-and-favors-release-of-viral-particles
#16
Regina Medvedev, Daniela Ploen, Catrina Spengler, Fabian Elgner, Huimei Ren, Sarah Bunten, Eberhard Hildt
Viruses are known to exploit the autophagic machinery for their own benefit. In case of the hepatitis C virus autophagy is induced. As autophagy serves as a degradation pathway to maintain cellular homeostasis, it is activated in response to cellular stress such as elevated levels of reactive oxygen species (ROS). Elevated levels of ROS trigger phosphorylation of the autophagic adaptor protein p62 on Ser349 (pS[349] p62) that is involved in the induction of autophagy. Consequently, pS[349] p62 binds with a higher affinity to Keap1 thereby releasing Nrf2 from the complex with Keap1...
June 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28669628/role-of-oxidative-stress-in-cardiovascular-disease-outcomes-following-exposure-to-ambient-air-pollution
#17
REVIEW
Frank J Kelly, Julia C Fussell
Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28669627/endogenous-hydrogen-sulfide-mediated-mapk-inhibition-preserves-endothelial-function-through-txnip-signaling
#18
Danyang Tian, Jinghui Dong, Sheng Jin, Xu Teng, Yuming Wu
Mounting evidence demonstrated deficient cystathionine-γ-lyase (CSE)/H2S implicated the development of cardiovascular disease. The present study aimed to evaluating the favorable action of CSE derived H2S on endothelial function in CSE(-/-) mice. CSE(-/-) mice exhibited attenuated endothelium-dependent relaxations, coupled with reduction of endothelial nitric oxide synthase (eNOS) phosphorylation at site of Ser1177, increase of thioredoxin interacting protein (TXNIP) level and MAPK phosphorylation, which were corrected by sodium hydrosulfide chronic treatment for 8 weeks...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28669626/metabolism-and-antioxidant-effect-of-malaxinic-acid-and-its-corresponding-aglycone-in-rat-blood-plasma
#19
Hyun Joo Lee, Hang Yeon Jeong, Mi Rim Jin, Hyoung Jae Lee, Jeong-Yong Cho, Jae-Hak Moon
Malaxinic acid (MA) is a phenolic acid compound, found mainly in pear fruits (Pyrus pyrifolia N.), that is isoprenylated on the C-3 position of benzoic acid. Recently, the effects of prenylated phenolics on health have received much interest owing to their reported potent beneficial biological effects. We conducted a comparative study in rats to determine the metabolism, pharmacokinetics, and antioxidative activities of MA and its corresponding aglycone (MAA). MA and MAA were orally administered to rats (Sprague-Dawley, male, 6 weeks old) and their metabolites in plasma were analyzed...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28666851/cold-atmospheric-plasma-restores-tamoxifen-sensitivity-in-resistant-mcf-7-breast-cancer-cell
#20
Seungyeon Lee, Hyunkyung Lee, Dawoon Jeong, Juyeon Ham, Sungbin Park, Eun Ha Choi, Sun Jung Kim
Cancer recurrence, which is frequently accompanied by chemotherapy, has been a challenge in cancer treatment. This study was carried out to examine the potential applications of the reactive oxygen species (ROS)-producing cold atmospheric plasma (CAP) to overcome the cancer cells' drug resistance, which has been emerging as an alternative therapeutic tool for cancer. For this, we developed a tamoxifen (Tam)-resistant MCF-7 (MCF-7/TamR) breast cancer cell model and examined the effect of CAP on the recovery of Tam sensitivity at the cellular and molecular level...
June 27, 2017: Free Radical Biology & Medicine
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