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https://www.readbyqxmd.com/read/28644409/quercetin-protects-obesity-induced-hypothalamic-inflammation-by-reducing-microglia-mediated-inflammatory-responses-via-ho-1-induction
#1
Jihyeon Yang, Chu-Sook Kim, Thai Hien Tu, Min-Seon Kim, Tsuyoshi Goto, Teruo Kawada, Myung-Sook Choi, Taesun Park, Mi-Kyung Sung, Jong Won Yun, Suck-Young Choe, Jee Hye Lee, Yeonsoo Joe, Hye-Seon Choi, Sung Hoon Back, Hun Taeg Chung, Rina Yu
Obesity-induced hypothalamic inflammation is characterized by activation of microglia, which are resident macrophages of the central nervous system, and is implicated in the derangement of energy homeostasis, metabolic complications, and neurodegenerative diseases. Quercetin, a naturally occurring flavonoid, is known to protect against oxidative stress and inflammation-related metabolic complications. Here, we demonstrate that quercetin reduces obesity-induced hypothalamic inflammation by inhibiting microglia-mediated inflammatory responses, and the beneficial action of quercetin is associated with heme oxygenase (HO-1) induction...
June 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28643828/adaptability-of-the-metal-iii-iv-1-2-3-trioxobenzene-rod-secondary-building-unit-for-the-production-of-chemically-stable-and-catalytically-active-mofs
#2
Georges Mouchaham, Brian Abeykoon, Mónica Giménez-Marqués, Sergio Navalon, Andrea Santiago-Portillo, Maame Affram, Nathalie Guillou, Charlotte Martineau, Hermenegildo Garcia, Alexandra Fateeva, Thomas Devic
The use of a 5,10,15,20-tetrakis(3,4,5-trihydroxyphenyl)porphyrin has yielded a new MOF based on M-1,2,3-trioxobenzene chains that can be made of M = Zr(iv) or RE(iii) (RE = rare earth), showing a very high and limited chemical stability, respectively. The robust metallated Zr-analogue, Co-MIL-173(Zr), has proven to be a heme-like heterogeneous catalyst suitable for aerobic oxidation of hydrocarbons.
June 23, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28642844/role-of-bacterioferritin-ferritin-in-m-tuberculosis-pathogenesis-and-drug-resistance-a-future-perspective-by-interactomic-approach
#3
Divakar Sharma, Deepa Bisht
Tuberculosis is caused by Mycobacterium tuberculosis, one of the most successful and deadliest human pathogen. Aminoglycosides resistance leads to emergence of extremely drug resistant strains of M. tuberculosis. Iron is crucial for the biological functions of the cells. Iron assimilation, storage and their utilization is not only involved in pathogenesis but also in emergence of drug resistance strains. We previously reported that iron storing proteins (bacterioferritin and ferritin) were found to be overexpressed in aminoglycosides resistant isolates...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642813/corrigendum-to-association-of-nuclear-factor-erythroid-2-related-factor-2-thioredoxin-interacting-protein-and-heme-oxygenase-1-gene-polymorphisms-with-diabetes-and-obesity-in-mexican-patients
#4
Angélica Saraí Jiménez-Osorio, Susana González-Reyes, Wylly Ramsés García-Niño, Hortensia Moreno-Macías, Martha Eunice Rodríguez-Arellano, Gilberto Vargas-Alarcón, Joaquín Zúñiga, Rodrigo Barquera, José Pedraza-Chaverri, Juan Pablo Meza-Espinoza, Evelia Leal-Ugarte, Valeria Peralta-Leal
[This corrects the article DOI: 10.1155/2016/7367641.].
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28642436/metalloprotein-entatic-control-of-ligand-metal-bonds-quantified-by-ultrafast-x-ray-spectroscopy
#5
Michael W Mara, Ryan G Hadt, Marco Eli Reinhard, Thomas Kroll, Hyeongtaek Lim, Robert W Hartsock, Roberto Alonso-Mori, Matthieu Chollet, James M Glownia, Silke Nelson, Dimosthenis Sokaras, Kristjan Kunnus, Keith O Hodgson, Britt Hedman, Uwe Bergmann, Kelly J Gaffney, Edward I Solomon
The multifunctional protein cytochrome c (cyt c) plays key roles in electron transport and apoptosis, switching function by modulating bonding between a heme iron and the sulfur in a methionine residue. This Fe-S(Met) bond is too weak to persist in the absence of protein constraints. We ruptured the bond in ferrous cyt c using an optical laser pulse and monitored the bond reformation within the protein active site using ultrafast x-ray pulses from an x-ray free-electron laser, determining that the Fe-S(Met) bond enthalpy is ~4 kcal/mol stronger than in the absence of protein constraints...
June 23, 2017: Science
https://www.readbyqxmd.com/read/28642370/in-vitro-cytochrome-p450-46a1-cyp46a1-activation-by-neuroactive-compounds
#6
Natalia Mast, Kyle W Anderson, Kevin M Johnson, Thanh T N Phan, F Peter Guengerich, Irina A Pikuleva
Cytochrome P450 46A1 (CYP46A1, cholesterol 24-hydroxylase) is the enzyme responsible for the majority of cholesterol elimination from the brain. Previously, we found that the anti-HIV drug efavirenz (EFV) can pharmacologically activate CYP46A1 in mice. Herein, we investigated whether CYP46A1 could also be activated by endogenous compounds, including major neurotransmitters. In vitro experiments with purified recombinant CYP46A1 indicated that CYP46A1 is activated by L-glutamate (L-Glu), L-aspartate, γ-aminobutyric acid, and acetylcholine, with L-Glu eliciting the highest increase (3-fold) in CYP46A1-mediated cholesterol 24-hydroxylation...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28641882/ferredoxin-dependent-bilin-reductases-in-eukaryotic-algae-ubiquity-and-diversity
#7
Nathan C Rockwell, J Clark Lagarias
Linear tetrapyrroles (bilins) are produced from heme by heme oxygenase, usually forming biliverdin IXα (BV). Fungi and bacteria use BV as chromophore for phytochrome photoreceptors. Oxygenic photosynthetic organisms use BV as a substrate for ferredoxin-dependent bilin reductases (FDBRs), enzymes that produce diverse reduced bilins used as light-harvesting pigments in phycobiliproteins and as photoactive photoreceptor chromophores. Bilin biosynthesis is essential for phototrophic growth in Chlamydomonas reinhardtii despite the absence of phytochromes or phycobiliproteins in this organism, raising the possibility that bilins are more generally required for phototrophic growth by algae...
May 31, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28641546/targeting-astrocytes-for-treating-neurological-disorders-carbon-monoxide-and-noradrenaline-induced-increase-in-lactate
#8
Anemari Horvat, Nina Vardjan, Robert Zorec
There are at least three reasons why brain astrocytes represent a new target for treating neurological disorders. First, although the human neocortex represents over 80% of brain mass, neurons are outnumbered by non-neuronal cells, including astrocytes, a neuroglial cell type. Second, as in neurons, vesicle-based release of transmitters is present in astrocytes, however with much slower kinetics than in neurons. Third, astrocytes contain glycogen, which can be transformed to L-lactate in glycolysis. L-lactate is considered to be a fuel and a signalling molecule involved in cognition and neuroprotection...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#9
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28639182/differential-interaction-of-myoglobin-with-select-fatty-acids-of-carbon-chain-lengths-c8-to-c16
#10
Thomas Jue, Lifan Shih, Youngran Chung
Previous studies have shown that palmitic acid (PAM) and oleic acid (OLE) can bind myoglobin (Mb). How fatty acids (FA) with different carbon chain lengths and sulfate substitution interact with Mb remains uncertain. Indeed, C8:0 and C10:0 fatty acids do not perturb the intensities of the (1)H-NMR MbCN signal intensity at FA:Mb ratios below 2:1. Starting with C12:0, C12:0-C16:0, FA induce a noticeable spectral change. C12:0 and C14:0 FA affect both the 5- and 8-heme methyl signals, whereas the C16:0 FA perturbs only the 8-heme methyl signal...
June 21, 2017: Lipids
https://www.readbyqxmd.com/read/28638761/peroxidase-activity-of-a-c-type-cytochrome%C3%A2-b5-in-the-non-native-state-is-comparable-to-that-of-native-peroxidases
#11
Shan Hu, Bo He, Ke-Jie Du, Xiao-Juan Wang, Shu-Qin Gao, Ying-Wu Lin
The design of artificial metalloenzymes has achieved tremendous progress, although few designs can achieve catalytic performances comparable to that of native enzymes. Moreover, the structure and function of artificial metalloenzymes in non-native states has rarely been explored. Herein, we found that a c-type cytochrome b5 (Cyt b5), N57C/S71C Cyt b5, with heme covalently attached to the protein matrix through two Cys-heme linkages, adopts a non-native state with an open heme site after guanidine hydrochloride (Gdn⋅HCl)-induced unfolding, which facilitates H2O2 activation and substrate binding...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28637874/direct-demonstration-of-a-neonatal-fc-receptor-fcrn-driven-endosomal-sorting-pathway-for-cellular-recycling-of-albumin
#12
Esben G W Schmidt, Michael L Hvam, Filipa Antunes, Jason Cameron, Dorthe Viuff, Birgitte Andersen, Nanna N Kristensen, Kenneth A Howard
Albumin is the most abundant plasma protein involved in the transport of many compounds, such as fatty acids, bilirubin, and heme. The endothelial cellular neonatal Fc receptor (FcRn) has been suggested to play a central role in maintaining the high albumin plasma levels through a cellular recycling pathway. However, direct mapping of this process is still lacking. This work presents the use of wild type and engineered recombinant albumins with either decreased or increased FcRn affinity in combination with a low or high FcRn-expressing endothelium cell line to clearly define the FcRn involvement, intracellular pathway and kinetics of albumin trafficking by flow cytometry, quantitative confocal microscopy, and an albumin-recycling assay...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637872/hydrogen-sulfide-modulates-eukaryotic-translation-initiation-factor-2%C3%AE-eif2%C3%AE-phosphorylation-status-in-the-integrated-stress-response-pathway
#13
Vinita Yadav, Xing-Huang Gao, Belinda Willard, Maria Hatzoglou, Ruma Banerjee, Omer Kabil
Hydrogen sulfide (H2S) regulates various physiological processes including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the transsulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response (ISR) promoting a metabolic state primed for stress response...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#14
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636034/upregulation-of-heme-oxygenase-1-mediates-the-anti-inflammatory-activity-of-casein-glycomacropeptide-gmp-hydrolysates-in-lps-stimulated-macrophages
#15
Tiange Li, Xue Cheng, Min Du, Bin Chen, Xueying Mao
Recently, we have shown that casein glycomacropeptide hydrolysates (GHP) exhibit both anti-inflammatory and anti-oxidative activities in vitro. However, whether heme oxygenase-1 (HO-1) is involved in the cytoprotective effect of GHP against the inflammatory status remains unclear. Therefore, we hypothesized that HO-1 is a potential target of GHP, which mediates its anti-inflammatory effect. Here, GHP inhibited the intracellular reactive oxygen species (ROS) accumulation and NADPH oxidase 2 (NOX2) expression and enhanced reduced glutathione (GSH) levels in LPS-stimulated RAW264...
June 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28635609/gastroprotective-effect-of-ghrelin-against-indomethacin-induced-gastric-injury-in-rats-possible-role-of-heme-oxygenase-1-pathway
#16
Mona M Allam, Ola A El-Gohary
Ghrelin has been shown to ameliorate gastric injury by several mechanisms in experimental animal models. The present study aimed to investigate the effect of pretreatment with ghrelin on indomethacin-induced gastric injury in rats and the role of heme oxygenase-1(HO-1) pathway as a novel mechanism underlying the gastroprotective effect of ghrelin. In all groups studied, ulcer score (U.S), ulcer index (U.I) and preventive index (P.I) were evaluated and the gastric inflammatory biomarkers including levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and myeloperoxidase (MPO) activity as well as prostaglandin E2 (PGE2), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), HO-1 and bilirubin as an indicator of heme oxygenase activity were measured...
July 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/28634389/novel-indolyl-chalcone-derivatives-inhibit-a549-lung-cancer-cell-growth-through-activating-nrf-2-ho-1-and-inducing-apoptosis-in-vitro-and-in-vivo
#17
Xuan Zhao, WenLiang Dong, YuanDi Gao, Dong-Shoo Shin, Qing Ye, Le Su, Fan Jiang, BaoXiang Zhao, JunYing Miao
Increasing evidence indicates that Nrf-2, named the nuclear factor-erythroid 2-related factor, may perform anticancer function. In this study, a series of novel substituted phenyl- (3-methyl-1H-indol-2-yl)-prop-2-en-1-one (indolyl-chalcone) derivatives were synthesized and their effects on Nrf-2 activity were observed. We found that compounds 3a-3d and 6c elevated Nrf-2 activity. Then we evaluated their anticancer activities in vitro and in vivo by utilizing human lung cancer cell line A549. The in vitro results showed that among the compounds, 3d performed effectively anti-growth activity by inducing A549 lung cancer cell apoptosis and activating Nrf-2/HO-1 (heme oxygenase-1) pathway...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634234/the-thioreduction-component-ccmg-confers-efficiency-and-the-heme-ligation-component-ccmh-ensures-stereo-specificity-during-cytochrome-c-maturation
#18
Andreia F Verisssimo, Bahia Khalfaoui-Hassani, Josephine Hwang, Stefan Steimle, Nur Selamoglu, Carsten Sanders, Camilo Khatchikian, Fevzi Daldal
In many Gram-negative bacteria, including Rhodobacter capsulatus, cytochrome c maturation (Ccm) is carried out by a membrane-integral machinery composed of nine proteins (CcmA to I). During this process, the periplasmic thiol-disulfide oxidoreductase DsbA is thought to catalyze the formation of a disulfide bond between the Cys residues at the apocytochrome c heme binding site (CXXCH). Subsequently, a Ccm-specific thioreductive pathway involving CcmG and CcmH reduces this disulfide bond to allow covalent heme ligation...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634178/ascorbate-protects-the-di-heme-enzyme-maug-against-self-inflicted-oxidative-damage-by-an-unusual-antioxidant-mechanism
#19
Zhongxin Ma, Victor L Davidson
Ascorbate protects MauG from self-inactivation that occurs during the autoreduction of the reactive bis -Fe(IV) state of its diheme cofactor. The mechanism of protection does not involve direct reaction with reactive oxygen species in solution. Instead it binds to MauG and mitigates oxidative damage that occurs via internal transfer of electrons from amino acid residues within the protein to the high-valent hemes. The presence of ascorbate does not inhibit the natural catalytic reaction of MauG which catalyzes oxidative posttranslational modifications of a substrate protein that binds to the surface of MauG, and is oxidized by the high-valent hemes via long range electron transfer...
June 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28634030/effects-of-membrane-curvature-and-ph-on-proton-pumping-activity-of-single-cytochrome-bo3-enzymes
#20
Mengqiu Li, Sanobar Khan, Honglin Rong, Roman Tuma, Nikos S Hatzakis, Lars J C Jeuken
The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from Escherichia coli, cytochrome bo3, for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055-16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P-side of single HCOs...
June 17, 2017: Biochimica et Biophysica Acta
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