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https://www.readbyqxmd.com/read/28157235/possible-involvement-of-nitric-oxide-in-enhanced-liver-injury-and-fibrogenesis-during-cholestasis-in-cytoglobin-deficient-mice
#1
Tuong Thi Van Thuy, Le Thi Thanh Thuy, Katsutoshi Yoshizato, Norifumi Kawada
This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells (HSCs), in cholestatic liver disease. Bile duct ligation (BDL) augmented inflammatory reactions as revealed by increased infiltrating neutrophils, CD68(+)-macrophages, and chemokine expression in Cygb(-/-) mice. In these mice, impairment of bile canalicular indicated by the loss of CD10 expression, down-regulation of bile salt transporters, increased total bile acid, and massive apoptotic and necrotic hepatocytes occurred with the release of cytochrome c, activation of caspase 3, resulting in reduced animal survival compared to wild-type mice...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128325/protective-effects-of-recombinant-human-cytoglobin-against-chronic-alcohol-induced-liver-disease-in-vivo-and-in-vitro
#2
Jian Wen, Yongbin Wu, Wei Wei, Zhen Li, Ping Wang, Shiwei Zhu, Wenqi Dong
Alcoholic liver disease (ALD) is an important worldwide public health issue with no satisfying treatment available since now. Here we explore the effects of recombinant human cytoglobin (rhCygb) on chronic alcohol-induced liver injury and the underlying mechanisms. In vivo studies showed that rhCygb was able to ameliorate alcohol-induced liver injury, significantly reversed increased serum index (ALT, AST, TG, TC and LDL-C) and decreased serum HDL-C. Histopathology observation of the liver of rats treated with rhCygb confirmed the biochemical data...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28099346/liuwei-dihuang-pill-treats-diabetic-nephropathy-in-rats-by-inhibiting-of-tgf-%C3%AE-smads-mapk-and-nf-kb-and-upregulating-expression-of-cytoglobin-in-renal-tissues
#3
Zhong Ju Xu, Shi Shu, Zhi Jie Li, Yu Min Liu, Rui Yi Zhang, Yue Zhang
Liuwei Dihuang pill (LDP) was assessed for its effects on renal deficiency.90 STZ induced DN rats were divided into groups (n = 22) without treatment (STZ) and LDP treated (STZ-L) (n = 23), Zhenwu decoction treated (STZ-Z) (n = 22), and valsartan treated (STZ-V) (n = 23) groups, with 16 normal control rats. Total urine protein (TP), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured. Superoxide dismutase (SOD), nitric oxide synthase (NOS), and malondialdehyde (MDA) concentrations as well as expression/phosphorylation of SMAD3, SMAD2, and α-SMA, TGF-β, RI /II, P38, ERK, and NF-kB in renal tissues were determined...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27928650/cytoglobin-a-potential-marker-for-adipogenic-differentiation-in-preadipocytes-in-vitro
#4
Ayşegül Doğan, Selami Demirci, Binnur Kıratlı, Fikrettin Şahin
Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated diseases. Discovery of new genes and proteins in the differentiation pathway could help to understand the key specific regulators of the adipogenesis. Cytoglobin (Cygb), identified as a new globin family member protein, is expressed in various tissues...
February 2017: Cytotechnology
https://www.readbyqxmd.com/read/27867483/brain-globins-in-physiology-and-pathology
#5
REVIEW
Luo-Kun Xie, Shao-Hua Yang
Globins are globular proteins for either transport or storage of oxygen which are critical for cellular metabolism. Four globins have been identified in rodent and human brains. Among them, neuroglobin, cytoglobin and hemoglobin chains are constitutively expressed in normal brain, while myoglobin is only expressed in some neurological disorders. Studies on the molecular structure, expression and functional features of these brain globins indicated that they may play crucial roles in maintenance of neural cell survival and activity, including neurons and astrocytes...
July 2016: Medical Gas Research
https://www.readbyqxmd.com/read/27678372/the-novel-thiosemicarbazone-di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone-dpc-inhibits-neuroblastoma-growth-in-vitro-and-in-vivo-via-multiple-mechanisms
#6
Zhu-Ling Guo, Des R Richardson, Danuta S Kalinowski, Zaklina Kovacevic, Kian Cheng Tan-Un, Godfrey Chi-Fung Chan
BACKGROUND: Neuroblastoma is a relatively common and highly belligerent childhood tumor with poor prognosis by current therapeutic approaches. A novel anti-cancer agent of the di-2-pyridylketone thiosemicarbazone series, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), demonstrates promising anti-tumor activity. Recently, a second-generation analogue, namely di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), has entered multi-center clinical trials for the treatment of advanced and resistant tumors...
September 27, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27637274/redox-and-peroxidase-activities-of-the-hemoglobin-superfamily-relevance-to-health-and-disease
#7
Brandon J Reeder
SIGNIFICANCE: Erythrocyte hemoglobin (Hb) and myocyte myoglobin, although primarily oxygen-carrying proteins, have the capacity to do redox chemistry. Such redox activity in the wider family of globins now appears to have important associations with the mechanisms of cell stress response. In turn, an understanding of such mechanisms in vivo may have a potential in the understanding of cancer therapy resistance and neurodegenerative disorders such as Alzheimer's. Recent Advances: There has been an enhanced understanding of the redox chemistry of the globin superfamily in recent years, leading to advances in development of Hb-based blood substitutes and in hypotheses relating to specific disease mechanisms...
October 20, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27512111/unusual-diversity-of-myoglobin-genes-in-the-lungfish
#8
Jonas Koch, Julia Lüdemann, Rieke Spies, Marco Last, Chris T Amemiya, Thorsten Burmester
Myoglobin is a respiratory protein that serves as a model system in a variety of biological fields. Its main function is to deliver and store O2 in the heart and skeletal muscles, but myoglobin is also instrumental in homeostasis of nitric oxide (NO) and detoxification of reactive oxygen species (ROS). Almost every vertebrate harbors a single myoglobin gene; only some cyprinid fishes have two recently duplicated myoglobin genes. Here we show that the West African lungfish Protopterus annectens has at least seven distinct myoglobin genes (PanMb1-7), which diverged early in the evolution of lungfish and showed an enhanced evolutionary rate...
December 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27496969/dna-hypermethylation-analysis-in-sputum-of-asymptomatic-subjects-at-risk-for-lung-cancer-participating-in-the-nelson-trial-argument-for-maximum-screening-interval-of-2%C3%A2-years
#9
A Jasmijn Hubers, Daniëlle A M Heideman, Sylvia Duin, Birgit I Witte, Harry J de Koning, Harry J M Groen, Clemens F M Prinsen, Anne S Bolijn, Mandy Wouters, Susanne E van der Meer, Renske D M Steenbergen, Peter J F Snijders, Anne Uyterlinde, Hans Berkhof, Egbert F Smit, Erik Thunnissen
AIMS: Lung cancer is the major contributor to cancer mortality due to metastasised disease at time of presentation. The current study investigated DNA hypermethylation of biomarkers RASSF1A, APC, cytoglobin, 3OST2, FAM19A4, PHACTR3 and PRDM14 in sputum of asymptomatic high-risk individuals from the NELSON lung cancer low-dose spiral CT screening trial to detect lung cancer at preclinical stage. METHODS: Subjects were selected with (i) lung cancer in follow-up (cases; n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random selection of subjects without cytological aberrations (controls; n=99)...
August 5, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27441981/evaluation-of-globins-expression-in-brain-heart-and-lung-in-rats-exposed-to-side-stream-cigarette-smoke
#10
Barbara Tae, Kelen Carneiro Oliveira, Rodrigo Rodrigues da Conceição, Vitor Engrácia Valenti, Janaina Sena de Souza, Roberto Laureano-Melo, Monica Akemi Sato, Rui Monteiro de Barros Maciel, Gisele Giannocco
The side stream cigarette smoke (SSCS) is a contributing factor in the pathogenesis of cigarette smoking-induced toxicity. Hemoglobin (Hb), myoglobin (Mb), neuroglobin (Ngb), and cytoglobin (Cygb) are globins with different distributions and functions in the tissues and have similar actions by providing O2 (oxygen) for respiratory chain, detoxification of ROS and nitric oxide (NO), and protect tissues against irreversible lesions. We aimed to investigate the effects of SSCS exposure on gene and protein expression of Ngb, Cygb, and Mb in different tissue...
July 21, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27431913/changes-in-mitochondrial-stability-during-the-progression-of-the-barrett-s-esophagus-disease-sequence
#11
N J O'Farrell, R Feighery, S L Picardo, N Lynam-Lennon, M Biniecka, S A McGarrigle, J J Phelan, F MacCarthy, D O'Toole, E J Fox, N Ravi, J V Reynolds, J O'Sullivan
BACKGROUND: Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair. The timing and levels of mitochondria instability and dysfunction across the Barrett's disease progression is under studied...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27407144/globin-x-is-a-six-coordinate-globin-that-reduces-nitrite-to-nitric-oxide-in-fish-red-blood-cells
#12
Paola Corti, Jianmin Xue, Jesús Tejero, Nadeem Wajih, Ming Sun, Donna B Stolz, Michael Tsang, Daniel B Kim-Shapiro, Mark T Gladwin
The discovery of novel globins in diverse organisms has stimulated intense interest in their evolved function, beyond oxygen binding. Globin X (GbX) is a protein found in fish, amphibians, and reptiles that diverged from a common ancestor of mammalian hemoglobins and myoglobins. Like mammalian neuroglobin, GbX was first designated as a neuronal globin in fish and exhibits six-coordinate heme geometry, suggesting a role in intracellular electron transfer reactions rather than oxygen binding. Here, we report that GbX to our knowledge is the first six-coordinate globin and the first globin protein apart from hemoglobin, found in vertebrate RBCs...
July 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27199679/distribution-of-cytoglobin-in-the-mouse-brain
#13
Stefan Reuss, Sylvia Wystub, Ursula Disque-Kaiser, Thomas Hankeln, Thorsten Burmester
Cytoglobin (Cygb) is a vertebrate globin with so far poorly defined function. It is expressed in the fibroblast cell-lineage but has also been found in neurons. Here we provide, using immunohistochemistry, a detailed study on the distribution of Cygb in the mouse brain. While Cygb is a cytoplasmic protein in active cells of the supportive tissue, in neurons it is located in the cytoplasm and the nucleus. We found the expression of Cygb in all brain regions, although only a fraction of the neurons was Cygb-positive...
2016: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/27146058/absence-of-cytoglobin-promotes-multiple-organ-abnormalities-in-aged-mice
#14
Le Thi Thanh Thuy, Tuong Thi Van Thuy, Yoshinari Matsumoto, Hoang Hai, Yoshihiro Ikura, Katsutoshi Yoshizato, Norifumi Kawada
Cytoglobin (Cygb) was identified in hepatic stellate cells (HSCs) and pericytes of all organs; however, the effects of Cygb on cellular functions remain unclear. Here, we report spontaneous and age-dependent malformations in multiple organs of Cygb(-/-) mice. Twenty-six percent of young Cygb(-/-) mice (<1 year old) showed heart hypertrophy, cystic disease in the kidney or ovary, loss of balance, liver fibrosis and lymphoma. Furthermore, 71.3% (82/115) of aged Cygb(-/-) mice (1-2 years old) exhibited abnormalities, such as heart hypertrophy and cancer development in multiple organs; by contrast, 5...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27006085/the-effect-of-rhcygb-on-ccl4-induced-hepatic-fibrogenesis-in-rat
#15
Zhen Li, Wei Wei, Bohong Chen, Gaotai Cai, Xin Li, Ping Wang, Jinping Tang, Wenqi Dong
This study aims to investigate whether the use of recombinant human cytoglobin (rhCygb) impact on hepatic fibrogenesis caused by CCl4. SD (n = 150) rats were randomly divided into three groups of normal, CCl4 model and rhCygb groups. After model establishment, rats in rhCygb groups were administered daily with rhCygb (2 mg/kg, s.c.). Histological lesions were staged according to metavir. Serum parameters including ALT, AST, HA, LN, Col III and Col IV were determined. The liver proteins were separated by 2-DE and identified...
March 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26972599/discovery-of-cytoglobin-and-its-roles-in-physiology-and-pathology-of-hepatic-stellate-cells
#16
REVIEW
Katsutoshi Yoshizato, Le Thi Thanh Thuy, Goshi Shiota, Norifumi Kawada
Cytoglobin (CYGB), a new member of the globin family, was discovered in 2001 as a protein associated with stellate cell activation (stellate cell activation-associated protein [STAP]). Knowledge of CYGB, including its crystal, gene, and protein structures as well as its physiological and pathological importance, has increased progressively. We investigated the roles of oxygen (O2)-binding CYGB as STAP in hepatic stellate cells (HSCs) to understand the part played by this protein in their pathophysiological activities...
2016: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/26928591/peroxidase-activation-of-cytoglobin-by-anionic-phospholipids-mechanisms-and-consequences
#17
Jesús Tejero, Alexandr A Kapralov, Matthew P Baumgartner, Courtney E Sparacino-Watkins, Tamil S Anthonymutu, Irina I Vlasova, Carlos J Camacho, Mark T Gladwin, Hülya Bayir, Valerian E Kagan
Cytoglobin (Cygb) is a hexa-coordinated hemoprotein with yet to be defined physiological functions. The iron coordination and spin state of the Cygb heme group are sensitive to oxidation of two cysteine residues (Cys38/Cys83) and/or the binding of free fatty acids. However, the roles of redox vs lipid regulators of Cygb's structural rearrangements in the context of the protein peroxidase competence are not known. Searching for physiologically relevant lipid regulators of Cygb, here we report that anionic phospholipids, particularly phosphatidylinositolphosphates, affect structural organization of the protein and modulate its iron state and peroxidase activity both conjointly and/or independently of cysteine oxidation...
May 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26841790/dynamic-features-of-carboxy-cytoglobin-distal-mutants-investigated-by-molecular-dynamics-simulations
#18
Cong Zhao, Weihong Du
Cytoglobin (Cgb) is a member of hemoprotein family with roles in NO metabolism, fibrosis, and tumourigenesis. Similar to other hemoproteins, Cgb structure and functions are markedly influenced by distal key residues. The sixth ligand His(81) (E7) is crucial to exogenous ligand binding, heme pocket conformation, and physiological roles of this protein. However, the effects of other key residues on heme pocket and protein biological functions are not well known. In this work, a molecular dynamics (MD) simulation study of two single mutants in CO-ligated Cgb (L46FCgbCO and L46VCgbCO) and two double mutants (L46FH81QCgbCO and L46VH81QCgbCO) was conducted to explore the effects of the key distal residues Leu(46)(B10) and His(81)(E7) on Cgb structure and functions...
April 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/26831729/convergent-evolution-of-hemoglobin-switching-in-jawed-and-jawless-vertebrates
#19
Kim Rohlfing, Friederike Stuhlmann, Margaret F Docker, Thorsten Burmester
BACKGROUND: During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). RESULTS: We identified three hemoglobin switches in the life cycle of the sea lamprey...
2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/26721561/characterization-of-zebrafish-neuroglobin-and-cytoglobins-1-and-2-zebrafish-cytoglobins-provide-insights-into-the-transition-from-six-coordinate-to-five-coordinate-globins
#20
Paola Corti, Matthew Ieraci, Jesús Tejero
Neuroglobin (Ngb) and cytoglobin (Cygb) are two six-coordinate heme proteins of unknown physiological function. Although studies on the mammalian proteins have elucidated aspects of Ngb and Cygb biophysics and indicated potential functions, the properties of non-mammalian Ngbs and Cygbs are largely uncharacterized. We have expressed the recombinant zebrafish proteins Ngb, Cygb1, and Cygb2 in Escherichia coli and characterized their nitrite reduction rates, spectral properties, autoxidation rate constants, redox potentials and lipid binding properties...
February 29, 2016: Nitric Oxide: Biology and Chemistry
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