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Free Radical Biology & Medicine

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https://www.readbyqxmd.com/read/28943453/titin-isoforms-are-increasingly-protected-against-oxidative-modifications-in-developing-rat-cardiomyocytes
#1
Beáta Bódi, EnikŐ Pásztorné Tóth, László Nagy, Attila Tóth, Lilla Mártha, Árpád Kovács, György Balla, Tamás Kovács, Zoltán Papp
During the perinatal adaptation process N2BA titin isoforms are switched for N2B titin isoforms leading to an increase in cardiomyocyte passive tension (Fpassive). Here we attempted to reveal how titin isoform composition and oxidative insults (i.e. sulfhydryl (SH)-group oxidation or carbonylation) influence Fpassive of left ventricular cardiomyocytes during rat heart development. Moreover, we also examined a hypothetical protective role for titin associated small heat shock proteins (sHSPs), Hsp27 and αB-crystallin in the above processes...
September 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28942246/inhibition-of-hepatocyte-nuclear-factor-1b-induces-hepatic-steatosis-through-dpp4-nox1-mediated-regulation-of-superoxide
#2
Zi Long, Meng Cao, Shuhao Su, Guangyuan Wu, Fansen Meng, Hao Wu, Jiangzheng Liu, Weihua Yu, Kamran Atabai, Xin Wang
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is closely associated with insulin resistance and type 2 diabetes. Previous studies have suggested that hepatocyte nuclear factor 1b (HNF1b) ameliorates insulin resistance. However, the role of HNF1b in the regulation of lipid metabolism and hepatic steatosis remains poorly understood. We found that HNF1b expression was decreased in steatotic livers. We injected mice with lentivirus (LV) expressing HNF1b shRNA to generate mice with hepatic knockdown of HNF1b...
September 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28942245/regulatory-role-of-nadph-oxidase-2-in-the-polarization-dynamics-and-neurotoxicity-of-microglia-macrophages-after-traumatic-brain-injury
#3
Jing Wang, Merry W Ma, Krishnan M Dhandapani, Darrell W Brann
Traumatic brain injury (TBI) is a leading cause of death and disability. Secondary injuries that develop after the initial trauma contribute to long-lasting neurophysiological deficits. Polarization of microglia/macrophages toward a pro-inflammatory (M1) phenotype may increase the progression of secondary injury following TBI; however, the regulatory and functional mechanisms underlying these changes remain poorly defined. In the present study, we showed elevated expression of NADPH oxidase 2 (NOX2) and activation of nuclear factor-kappa B (NF-κB) predominantly in microglia/macrophages at 4- and 7-days after controlled cortical impact in mice...
September 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28939422/suppressed-ubiquitination-of-nrf2-by-p47-phox-contributes-to-nrf2-activation
#4
Kyun Ha Kim, Ruxana T Sadikot, Ji Yeon Lee, Han-Sol Jeong, Yu-Kyoung Oh, Timothy S Blackwell, Myungsoo Joo
Although critical in phagocytosis in innate immunity, reactive oxygen species (ROS) collaterally inflict damage to host phagocytes because they indiscriminate targets. Since Nrf2 increases the expression of anti-oxidant enzymes that nullifies ROS, ROS activating Nrf2 is a critical negative regulatory step for countering the deleterious effects of ROS. Here, we postulate whether, along with ROS activating Nrf2, NADPH oxidase components also participate in direct activation of Nrf2, contributing to protection from ROS...
September 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28939421/theaflavin-ameliorates-ionizing-radiation-induced-hematopoietic-injury-via-the-nrf2-pathway
#5
Xiaodan Han, Junling Zhang, Xiaolei Xue, Yu Zhao, Lu Lu, Ming Cui, Weimin Miao, Saijun Fan
It has been well established that reactive oxygen species (ROS) play a critical role in ionizing radiation (IR)-induced hematopoietic injury. Theaflavin (TF), a polyphenolic compound from black tea, has been implicated in the regulation of endogenous cellular antioxidant systems. However, it remains unclear whether TF could ameliorate IR-induced hematopoietic injury, particularly the hematopoietic stem cell (HSC) injury. In this study, we explored the potential role of TF in IR-induced HSC injury and the underlying mechanism in a total body irradiation (TBI) mouse model...
September 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28935420/down-syndrome-beta-amyloid-and-neuroimaging
#6
REVIEW
Elizabeth Head, Alex Helman, David Powell, Frederick Schmitt
This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here...
September 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28935419/red-near-infrared-light-stimulates-release-of-an-endothelium-dependent-vasodilator-and-rescues-vascular-dysfunction-in-a-diabetes-model
#7
Agnes Keszler, Brian Lindemer, Dorothee Weihrauch, Deron Jones, Neil Hogg, Nicole L Lohr
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm(2) for 5min with 10min dark period)...
September 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#8
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916473/down-regulation-of-nox2-activity-in-phagocytes-mediated-by-atm-kinase-dependent-phosphorylation
#9
Sylvain Beaumel, Antoine Picciocchi, Franck Debeurme, Corinne Vivès, Anne-Marie Hesse, Myriam Ferro, Didier Grunwald, Heather Stieglitz, Pahk Thepchatri, Susan M E Smith, Franck Fieschi, Marie José Stasia
NADPH oxidases (NOX) have many biological roles, but their regulation to control production of potentially toxic ROS molecules remains unclear. A previously identified insertion sequence of 21 residues (called NIS) influences NOX activity, and its predicted flexibility makes it a good candidate for providing a dynamic switch controlling the NOX active site. We constructed NOX2 chimeras in which NIS had been deleted or exchanged with those from other NOXs (NIS1, 3 and 4). All contained functional heme and were expressed normally at the plasma membrane of differentiated PLB-985 cells...
September 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#10
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916475/deletion-of-nadh-oxidase-in-listeria-monocytogenes-promotes-the-bacterial-infection-of-brain
#11
Sen Li, Wenwen Yu, Xiao Guan, Zhen Luo, Guowei Chen, Wukang Liu, Jingchen Zhang
NADH oxidase (NOX) plays important roles in respiration and reactive oxygen species (ROS) generation in cells. In this study, we explored the function of NOX in Listeria monocytogenes by gene deletion. From our results, nox mutant strain (∆nox) had lower H2O2 level and showed no significant alteration in bacteria growth activity. But it had enhanced invasiveness during the invasion of glial cells and mice brain compared to wildtype strain. Furthermore, several virulence genes involved in invasion, such as inlA, inlB, vip and sigB, were upregulated in ∆nox, and the alterations could be restored by complementation...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916474/nox4-regulates-the-enos-uncoupling-process-in-aging-endothelial-cells
#12
Hwa-Young Lee, Hafiz Maher Ali Zeeshan, Hyung-Ryong Kim, Han-Jung Chae
ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chaperone were highly activated, and the resultant ER redox imbalance leads to disturbance of protein folding capability, namely endoplasmic reticulum (ER) stress, ultimately inducing dissociation between HSP90 and IRE-1α or PERK, decreasing HSP90 stability and dissociating the binding of eNOS from the HSP90 and leading to eNOS uncoupling...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916472/characterizing-thiol-redox-dynamics-in-the-organogenesis-stage-rat-embryo
#13
K Veltman, Y Ahmad, C Harris, O Jolliet
Precise control of the glutathione (GSH):glutathione disulfide (GSSG) balance is vital for the developing embryo, but it is not yet well understood how GSH levels and the GSH redox state are regulated, maintained, and modulated over the course of mammalian embryonic development. In this study, we characterize and connect thiol redox dynamics, protein synthesis, volumetric growth and net cysteine fluxes over the course of early organogenesis (gestational day (GD) 10 to GD11.13) in the rat embryo. Our results show that despite a significant exponential growth of conceptal volumes and protein mass, the GSH:GSSG redox balance is remarkably stable during early organogenesis, with distinct redox potentials for the visceral yolk sac (VYS) (-218mV) and the embryo proper (EMB) (-222mV)...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#14
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28899725/nitric-oxide-donor-ru-terpy-bdq-no-3-induces-uncoupling-and-phosphorylation-of-endothelial-nitric-oxide-synthase-promoting-oxidant-production
#15
Simone R Potje, Zhenlong Chen, Suellen D'Arc S Oliveira, Lusiane M Bendhack, Roberto S da Silva, Marcelo G Bonini, Cristina Antoniali, Richard D Minshall
[Ru(terpy)(bdq)NO](3+) (TERPY) is a nitric oxide (NO) donor that promotes relaxation of the mesenteric artery and aorta in rats. We sought to investigate whether it acts as both an NO donor and endothelial NO synthase (eNOS) activator, as shown previously for nitroglycerin. Human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 cells transfected with empty vector (HEK) or eNOS cDNA (HEK-eNOS) were treated with TERPY (1µM) for different lengths of time. eNOS expression, dimerization, and Ser(1177) phosphorylation, caveolin-1 (Cav-1) oligomerization, Cav-1 Tyr(14) phosphorylation were evaluated by Western blotting...
September 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28893626/low-density-lipoprotein-docosahexaenoic-acid-nanoparticles-induce-ferroptotic-cell-death-in-hepatocellular-carcinoma
#16
Weijun Ou, Rohit S Mulik, Arnida Anwar, Jeffrey G McDonald, Xiaoshun He, Ian R Corbin
Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines. Following LDL-DHA treatment both rat and human HCC cells experience pronounced lipid peroxidation, depletion of glutathione and inactivation of the lipid antioxidant glutathione peroxidase-4 (GPX4) prior to cell death...
September 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28888620/the-caspase-8-bid-cytochrome-c-axis-links-signals-from-death-receptors-to-mitochondrial-reactive-oxygen-species-production
#17
Wan-Sung Kim, Kwang-Soon Lee, Ji-Hee Kim, Chun-Ki Kim, Gwangsoo Lee, Jongseon Choe, Moo-Ho Won, Tae-Hyoung Kim, Dooil Jeoung, Hansoo Lee, Ji-Yoon Kim, Mi Ae Jeong, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Ligation of the death receptors for TNF-α, FasL, and TRAIL triggers two common pathways, caspase-dependent intrinsic apoptosis and intracellular reactive oxygen species (ROS) generation. The apoptotic pathway is well characterized; however, a signaling linker between the death receptor and ROS production has not been clearly elucidated. Here, we found that death receptor-induced ROS generation was strongly inhibited by mitochondrial complex I and II inhibitors, but not by inhibitors of NADPH oxidase, lipoxygenase, cyclooxygenase or xanthine oxidase, indicating that ROS are mostly generated by the impairment of the mitochondrial respiratory chain...
September 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28882786/exosomal-biomarkers-in-down-syndrome-and-alzheimer-s-disease
#18
REVIEW
Eric D Hamlett, Aurélie Ledreux, Huntington Potter, Heidi J Chial, David Patterson, Joaquin M Espinosa, Brianne M Bettcher, Ann-Charlotte Granholm
Every person with Down syndrome (DS) has the characteristic features of Alzheimer's disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood...
September 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28877508/the-no-heme-signaling-hypothesis
#19
Andrei L Kleschyov
While the biological role of nitric oxide (NO) synthase (NOS) is appreciated, several fundamental aspects of the NOS/NO-related signaling pathway(s) remain incompletely understood. Canonically, the NOS-derived NO diffuses through the (inter)cellular milieu to bind the prosthetic ferro(Fe(2+))-heme group of the soluble guanylyl cyclase (sGC). The formation of ternary NO-ferroheme-sGC complex results in the enzyme activation and accelerated production of the second messenger, cyclic GMP. This paper argues that cells dynamically generate mobile/exchangeable NO-ferroheme species, which activate sGC and regulate the function of some other biomolecules...
September 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28870522/poly-i-c-impairs-no-donor-induced-relaxation-by-overexposure-to-no-via-the-nf-kappa-b-inos-pathway-in-rat-superior-mesenteric-arteries
#20
Makoto Ando, Takayuki Matsumoto, Kumiko Taguchi, Tsuneo Kobayashi
Recent studies have suggested a link between vascular dysfunction and innate immune activation including toll-like receptors (TLRs), but the detailed mechanism remains unclear. Here we investigated whether poly (I:C) [a synthetic double-strand RNA recognized by TLR3, melanoma differentiation-associated gene 5 (MDA5), and retinoic acid-inducible gene I (RIG-I)] affected nitric oxide (NO)/cGMP-related vascular relaxation, one of the major cascades of relaxation, in rat superior mesenteric arteries. Using organ-cultured arteries, we found that poly (I:C) (30μg/mL for approximately 1 day) markedly reduced sodium nitroprusside (SNP)-induced relaxation (vs...
September 1, 2017: Free Radical Biology & Medicine
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