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https://www.readbyqxmd.com/read/27906108/heme-oxygenase-and-carbon-monoxide-protect-from-muscle-dystrophy
#1
Mun Chun Chan, Olivia Ziegler, Laura Liu, Glenn C Rowe, Saumya Das, Leo E Otterbein, Zoltan Arany
BACKGROUND: Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. METHODS: Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy...
November 28, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27901057/digital-gene-expression-profiling-analysis-of-duodenum-transcriptomes-in-sd-rats-administered-ferrous-sulfate-or-ferrous-glycine-chelate-by-gavage
#2
Zhao Zhuo, Shenglin Fang, Qiaoling Hu, Danping Huang, Jie Feng
The absorption of different iron sources is a trending research topic. Many studies have revealed that organic iron exhibits better bioavailability than inorganic iron, but the concrete underlying mechanism is still unclear. In the present study, we examined the differences in bioavailability of ferrous sulfate and ferrous glycinate in the intestines of SD rats using Illumina sequencing technology. Digital gene expression analysis resulted in the generation of almost 128 million clean reads, with expression data for 17,089 unigenes...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899766/examining-potential-side-effects-of-therapeutic-hypothermia-in-experimental-intracerebral-hemorrhage
#3
Shannon Wowk, Kelly J Fagan, Yonglie Ma, Helen Nichol, Frederick Colbourne
Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH's anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11-72 h) or normothermia. We used X-ray fluorescence imaging to spatially quantify total and peri-hematoma iron three days post-injury. At three and seven days, we measured non-heme iron levels...
November 29, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27888129/iron-metabolism-modulation-in-atlantic-salmon-infested-with-the-sea-lice-lepeophtheirus-salmonis-and-caligus-rogercresseyi-a-matter-of-nutritional-immunity
#4
Valentina Valenzuela-Muñoz, Cristian Gallardo-Escárate
Sea lice are copepodid ectoparasites that produce high economic losses and environmental issues, thus impacting the salmon aquaculture worldwide. Atlantic salmon (Salmo salar) from Northern and Southern Hemispheres are primarily parasitized by Lepeophtheirus salmonis and Caligus rogercresseyi, respectively. To cope L. salmonis infestation, studies suggest that Atlantic salmon can restrict iron availability as a mechanism of nutritional immunity. However, no molecular studies of iron regulation from salmonids infected with C...
November 22, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27885368/structural-characterization-of-eash-aspergillus-japonicus-an-oxidase-involved-in-cycloclavine-biosynthesis
#5
Dorota Jakubczyk, Lorenzo Caputi, Clare E M Stevenson, David M Lawson, Sarah E O'Connor
Aj_EasH is a non-heme iron- and α-keto-glutarate-dependent oxidase that is responsible for an unusual cyclopropyl ring formation in the biosynthesis of the fungal ergot alkaloid cycloclavine. The three dimensional structure of Aj_EasH (2.2 Å resolution) reported here provides insight into the mechanism of this unusual and complex reaction.
November 25, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27867098/ammonia-promotes-endothelial-cell-survival-via-the-heme-oxygenase-1-mediated-release-of-carbon-monoxide
#6
Xiao-Ming Liu, Kelly J Peyton, William Durante
Although endothelial cells produce substantial quantities of ammonia during cell metabolism, the physiologic role of this gas in these cells is not known. In this study, we investigated if ammonia regulates the expression of heme oxygenase-1 (HO-1), and if this enzyme influences the biological actions of ammonia on endothelial cells. Exogenously administered ammonia, given as ammonium chloride or ammonium hydroxide, or endogenously generated ammonia stimulated HO-1 protein expression in cultured human and murine endothelial cells...
November 17, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27864463/increased-brain-hemopexin-levels-improve-outcomes-after-intracerebral-hemorrhage
#7
Jenna L Leclerc, Juan Santiago-Moreno, Alex Dang, Andrew S Lampert, Pedro E Cruz, Awilda M Rosario, Todd E Golde, Sylvain Doré
Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes...
November 18, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27864296/a-mechanistic-investigation-of-thrombotic-microangiopathy-associated-with-intravenous-abuse-of-opana-er
#8
Ryan Hunt, Ayla Yalamanoglu, James Tumlin, Tal Schiller, Jin Hyen Baek, Andrew Wu, Agnes B Fogo, Haichun Yang, Edward Wong, Peter Miller, Paul W Buehler, Chava Kimchi-Sarfaty
Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following intravenous abuse of extended release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of three patients and investigate intravenous exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high molecular weight polyethylene oxide (HMW PEO)...
November 18, 2016: Blood
https://www.readbyqxmd.com/read/27863031/discovery-of-novel-scaffold-as-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-based-on-pyrrolopiperazinone-alkaloid-longamide-b
#9
Zenyu Shiokawa, Emi Kashiwabara, Daisuke Yoshidome, Koichi Fukase, Shinsuke Inuki, Yukari Fujimoto
Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, since IDO1 play a critical role in escape of tumor cells from immune system. Herein we report that pyrrolopiperazinone alkaloid, longamide B, and its derivatives were identified as novel IDO1 inhibitors based on docking study and small library synthesis. The derivatives of longamide B, such as phenylamide derivative and thioamide derivative, showed higher IDO1 inhibitory activity than longamide B. The thioamide derivative, in particular, displayed an activity comparable to that of a representative IDO1 inhibitor, 1-methyl-tryptophan...
November 11, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27862990/effects-of-ferric-citrate-supplementation-on-advanced-glycation-end-products-in-a-rat-model-of-streptozotocin-nicotinamide-induced-diabetes
#10
Kuo-Ching Chao, Seu-Hwa Chen, Chun-Chao Chang, Yu-Chieh Lee, Chi-Mei Wang, Jung-Su Chang
SCOPE: Diabetes is associated with increased risks of anemia and activation of advanced glycation end products (AGEs) and the receptor for AGEs (RAGE). However, the effects of pharmacological doses of iron supplementation on AGE metabolism are less clear. The aim was to investigate the effect of ferric citrate supplementation on AGE metabolism. METHODS AND RESULTS: Diabetes was induced in overnight starved rats by intraperitoneal injections of 40 mg/kg streptozotocin and 120 mg/kg nicotinamide...
November 10, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27857815/the-role-of-the-iron-stain-in-assessing-intracranial-hemorrhage
#11
Rudy J Castellani, Gruschenka Mojica, George Perry
The timing of the breakdown of red blood cells and organization of hemorrhage has significance in the catabolism of heme and the processing of iron, but also has a practical application in terms of assigning, or attempting to assign, a time course with respect to traumatic events (e.g. contusions and hemorrhages). Attempts to date contusions, however, have generally been unsuccessful by macroscopic observation, whereas the microscopic observations provide broad data but are also anatomically imprecise as a function of time...
2016: Open Neurology Journal
https://www.readbyqxmd.com/read/27856345/drug-targeting-of-heme-proteins-in-mycobacterium-tuberculosis
#12
REVIEW
Kirsty J McLean, Andrew W Munro
TB, caused by the human pathogen Mycobacterium tuberculosis (Mtb, causes more deaths than any other infectious disease. Iron is crucial for Mtb to infect the host and to sustain infection, with Mtb encoding large numbers of iron-binding proteins. Many of these are hemoproteins with key roles, including defense against oxidative stress, cellular signaling and regulation, host cholesterol metabolism, and respiratory processes. Various heme enzymes in Mtb are validated drug targets and/or products of genes essential for bacterial viability or survival in the host...
November 14, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27855198/identification-and-characterization-of-a-new-protein-isoform-of-human-5-lipoxygenase
#13
Ann-Kathrin Häfner, Kim Beilstein, Philipp Graab, Ann-Katrin Ball, Meike J Saul, Bettina Hofmann, Dieter Steinhilber
Leukotrienes (LTs) are inflammatory mediators that play a pivotal role in many diseases like asthma bronchiale, atherosclerosis and in various types of cancer. The key enzyme for generation of LTs is the 5-lipoxygenase (5-LO). Here, we present a novel putative protein isoform of human 5-LO that lacks exon 4, termed 5-LOΔ4, identified in cells of lymphoid origin, namely the Burkitt lymphoma cell lines Raji and BL41 as well as primary B and T cells. Deletion of exon 4 does not shift the reading frame and therefore the mRNA is not subjected to non-mediated mRNA decay (NMD)...
2016: PloS One
https://www.readbyqxmd.com/read/27851935/reaction-intermediates-and-molecular-mechanism-of-peroxynitrite-activation-by-no-synthases
#14
Jérôme Lang, Amandine Maréchal, Manon Couture, Jérôme Santolini
The activation of the peroxynitrite anion (PN) by hemoproteins, which leads to its detoxification or, on the contrary to the enhancement of its cytotoxic activity, is a reaction of physiological importance that is still poorly understood. It has been known for some years that the reaction of hemoproteins, notably cytochrome P450, with PN leads to the buildup of an intermediate species with a Soret band at ∼435 nm (I435). The nature of this intermediate is, however, debated. On the one hand, I435 has been presented as a compound II species that can be photoactivated to compound I...
November 15, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27844077/fe-oxy-adducts-of-heme-a%C3%AE-and-heme-hiapp-complexes-intermediates-in-ros-generation
#15
Manas Seal, Soumya Mukherjee, Somdatta Ghosh Dey
Iron (Fe) is the most abundant transition metal ion in the human body and its role, in the form of heme, has been implicated in Alzheimer's disease (AD) and type 2 diabetes mellitus (T2Dm). Heme binds both amyloid beta (Aβ) and human islet amyloid polypeptide (hIAPP) to form heme-Aβ and heme-hIAPP complexes, respectively, and form reactive oxygen species (ROS) like H2O2, O2˙(-)etc., which are known to cause oxidative damage. However the intermediates involved during ROS formation have not yet been isolated...
November 15, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27832188/melatonin-receptor-agonists-as-the-perioceutics-agents-for-periodontal-disease-through-modulation-of-porphyromonas-gingivalis-virulence-and-inflammatory-response
#16
Wei Zhou, Xuan Zhang, Cai-Lian Zhu, Zhi-Yan He, Jing-Ping Liang, Zhong-Chen Song
AIM: "Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation...
2016: PloS One
https://www.readbyqxmd.com/read/27825993/methylglyoxal-modification-enhances-the-stability-of-hemoglobin-and-lowers-its-iron-mediated-oxidation-reactions-an-in-vitro-study
#17
Sauradipta Banerjee, Abhay Sankar Chakraborti
Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the present study, we have investigated the in vitro effect of methylglyoxal (200, 300μM) on the heme protein hemoglobin (HbA0) (100μM) after incubation for one week at 25°C...
November 5, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27821769/protein-aggregation-as-a-cellular-response-to-oxidative-stress-induced-by-heme-and-iron
#18
Luiz R C Vasconcellos, Fabianno F Dutra, Mariana S Siqueira, Heitor A Paula-Neto, Jennifer Dahan, Ellen Kiarely, Leticia A M Carneiro, Marcelo T Bozza, Leonardo H Travassos
Hemolytic diseases include a variety of conditions with diverse etiologies in which red blood cells are destroyed and large amounts of hemeproteins are released. Heme has been described as a potent proinflammatory molecule that is able to induce multiple innate immune responses, such as those triggered by TLR4 and the NLRP3 inflammasome, as well as necroptosis in macrophages. The mechanisms by which eukaryotic cells respond to the toxic effects induced by heme to maintain homeostasis are not fully understood, however...
November 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27818378/transgenic-tobacco-lines-expressing-sense-or-antisense-ferrochelatase-1-rna-show-modified-ferrochelatase-activity-in-roots-and-provide-experimental-evidence-for-dual-localization-of-ferrochelatase-1
#19
Daniel Hey, Patricia Ortega-Rodes, Tingting Fan, Florian Schnurrer, Lea Brings, Boris Hedtke, Bernhard Grimm
In plants, two genes encode ferrochelatase (FC), which catalyzes iron chelation into protoporphyrin IX at the final step of heme biosynthesis. FERROCHELATASE1 (FC1) is continuously, but weakly expressed in roots and leaves, while FC2 is dominantly active in leaves. As a continuation of previous studies on the physiological consequences of FC2 inactivation in tobacco, we aimed to assign FC1 function in plant organs. While reduced FC2 expression leads to protoporphyrin IX accumulation in leaves, FC1 down-regulation and overproduction caused reduced and elevated FC activity in root tissue, respectively, but were not associated with changes in macroscopic phenotype, plant development or leaf pigmentation...
October 22, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27818337/novel-insights-into-the-response-of-atlantic-salmon-salmo-salar-to-piscirickettsia-salmonis-interplay-of-coding-genes-and-lncrnas-during-bacterial-infection
#20
Diego Valenzuela-Miranda, Cristian Gallardo-Escárate
Despite the high prevalence and impact to Chilean salmon aquaculture of the intracellular bacterium Piscirickettsia salmonis, the molecular underpinnings of host-pathogen interactions remain unclear. Herein, the interplay of coding and non-coding transcripts has been proposed as a key mechanism involved in immune response. Therefore, the aim of this study was to evidence how coding and non-coding transcripts are modulated during the infection process of Atlantic salmon with P. salmonis. For this, RNA-seq was conducted in brain, spleen, and head kidney samples, revealing different transcriptional profiles according to bacterial load...
December 2016: Fish & Shellfish Immunology
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