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https://www.readbyqxmd.com/read/29296942/gene-edited-pseudogene-resurrection-corrects-p47phox-deficient-chronic-granulomatous-disease
#1
Randall K Merling, Douglas B Kuhns, Colin L Sweeney, Xiaolin Wu, Sandra Burkett, Jessica Chu, Janet Lee, Sherry Koontz, Giovanni Di Pasquale, Sandra A Afione, John A Chiorini, Elizabeth M Kang, Uimook Choi, Suk See De Ravin, Harry L Malech
Pseudogenes are duplicated genes with mutations rendering them nonfunctional. For single-gene disorders with homologous pseudogenes, the pseudogene might be a target for genetic correction. Autosomal-recessive p47phox-deficient chronic granulomatous disease (p47-CGD) is a life-threatening immune deficiency caused by mutations in NCF1, a gene with 2 pseudogenes, NCF1B and NCF1C. The most common NCF1 mutation, a GT deletion (ΔGT) at the start of exon 2 (>90% of alleles), is constitutive to NCF1B and NCF1C...
January 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29229188/plasmodium-p47-a-key-gene-for-malaria-transmission-by-mosquito-vectors
#2
REVIEW
Alvaro Molina-Cruz, Gaspar E Canepa, Carolina Barillas-Mury
Malaria is caused by infection with Plasmodium parasites that have a complex life cycle. The parasite protein P47 is critical for disease transmission. P47 mediates mosquito immune evasion in both Plasmodium berghei (Pbs47) and Plasmodium falciparum (Pfs47), and has been shown to be important for optimal female gamete fertility in P. berghei. Pfs47 presents strong geographic structure in natural P. falciparum populations, consistent with natural selection of Pfs47 haplotypes by the mosquito immune system as the parasite adapted to new vector species worldwide...
December 8, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29192236/estrogen-attenuates-agtr1-expression-to-reduce-pancreatic-%C3%AE-cell-death-from-high-glucose
#3
Suwattanee Kooptiwut, Keerati Wanchai, Namoiy Semprasert, Chatchawan Srisawat, Pa-Thai Yenchitsomanus
Chronic exposure of pancreatic β-cells to high glucose levels results in β-cell dysfunction and death. These effects can be protected by estrogen. The local pancreatic renin-angiotensin system (RAS) has been shown as a novel pathological pathway of high-glucose-induced cell death. The effect of estrogen on pancreatic RAS is still unknown. This study examines whether estrogen protects against pancreatic β-cell death caused by glucotoxicity via a decrease in the pancreatic β-cell RAS pathway. When INS-1 cells were cultured in a high glucose medium, cell death was significantly higher than when the cells were cultured in a basal glucose medium; similarly, there were also higher levels of AGTR1 and p47 ph ° x mRNA, and protein expression...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183727/resveratrol-strongly-enhances-the-retinoic-acid-induced-superoxide-generating-activity-via-up-regulation-of-gp91-phox-gene-expression-in-u937%C3%A2-cells
#4
Hidehiko Kikuchi, Hitomi Mimuro, Futoshi Kuribayashi
The membrane bound cytochrome b558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O2-)-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O2--generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O2--generating activity increased more than 5-fold compared with that in the absence of the latter...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#5
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αMβ2, but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b(-/-) microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47(phox) and superoxide production...
November 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/29135572/long-term-observational-studies-of-chronic-granulomatous-disease
#6
Maria Kanariou, Kleopatra Spanou, Sofia Tantou
PURPOSE OF REVIEW: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients...
November 10, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29081748/coq10-augments-rosuvastatin-neuroprotective-effect-in-a-model-of-global-ischemia-via-inhibition-of-nf-%C3%AE%C2%BAb-jnk3-bax-and-activation-of-akt-foxo3a-bim-cues
#7
Sarah A Abd El-Aal, Mai A Abd El-Fattah, Hanan S El-Abhar
Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29079525/conversion-of-nox2-into-a-constitutive-enzyme-in-vitro-and-in-living-cells-after-its-binding-with-a-chimera-of-the-regulatory-subunits
#8
Rawand Masoud, Xavier Serfaty, Marie Erard, Paul Machillot, Gilda Karimi, Elodie Hudik, Frank Wien, Laura Baciou, Chantal Houée-Levin, Tania Bizouarn
During the phagocytosis of pathogens by phagocyte cells, the NADPH oxidase complex is activated to produce superoxide anion, a precursor of microbial oxidants. The activated NADPH oxidase complex from phagocytes consists in two transmembrane proteins (Nox2 and p22(phox)) and four cytosolic proteins (p40(phox), p47(phox), p67(phox) and Rac1-2). In the resting state of the cells, these proteins are dispersed in the cytosol, the membrane of granules and the plasma membrane. In order to synchronize the assembly of the cytosolic subunits on the membrane components of the oxidase, a fusion of the cytosolic proteins p47(phox), p67(phox) and Rac1 named trimera was constructed...
October 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29069584/dendritic-cell-amiloride-sensitive-channels-mediate-sodium-induced-inflammation-and-hypertension
#9
Natalia R Barbaro, Jason D Foss, Dmytro O Kryshtal, Nikita Tsyba, Shivani Kumaresan, Liang Xiao, Raymond L Mernaugh, Hana A Itani, Roxana Loperena, Wei Chen, Sergey Dikalov, Jens M Titze, Bjorn C Knollmann, David G Harrison, Annet Kirabo
Sodium accumulates in the interstitium and promotes inflammation through poorly defined mechanisms. We describe a pathway by which sodium enters dendritic cells (DCs) through amiloride-sensitive channels including the alpha and gamma subunits of the epithelial sodium channel and the sodium hydrogen exchanger 1. This leads to calcium influx via the sodium calcium exchanger, activation of protein kinase C (PKC), phosphorylation of p47(phox), and association of p47(phox) with gp91(phox). The assembled NADPH oxidase produces superoxide with subsequent formation of immunogenic isolevuglandin (IsoLG)-protein adducts...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29043330/procyanidins-extracted-from-the-litchi-pericarp-ameliorate-atherosclerosis-in-apoe-knockout-mice-their-effects-on-nitric-oxide-bioavailability-and-oxidative-stress
#10
Shuang Rong, Xueting Hu, Siqi Zhao, Yanting Zhao, Xiao Xiao, Wei Bao, Liegang Liu
Epidemiological studies strongly support the role of procyanidin-rich beverages and fruit in the prevention of cardiovascular diseases. Procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins, were isolated and identified in our laboratory and have been proven to possess strong antioxidant activity in vitro. In the present study, we investigated the anti-atherosclerotic effects of LPPC in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet for 24 weeks. LPPC (100 mg kg(-1) body mass daily) significantly reduced the atherosclerotic lesion size (P < 0...
October 18, 2017: Food & Function
https://www.readbyqxmd.com/read/29042313/the-hypothetical-protein-p47-of-clostridium-botulinum-e1-strain-beluga-has-a-structural-topology-similar-to-bactericidal-permeability-increasing-protein
#11
Kwok-Ho Lam, Ruifeng Qi, Shun Liu, Amelie Kroh, Guorui Yao, Kay Perry, Andreas Rummel, Rongsheng Jin
Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening disease botulism. They are naturally produced by species of the bacteria Clostridium botulinum as stable and non-covalent complexes, in which the BoNT molecule is assembled with several auxiliary non-toxic proteins. Some BoNT serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced by Clostridium strains that carry the ha gene cluster, which encodes four neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an important role to deliver and protect BoNTs in the gastrointestinal tract during oral intoxication...
October 16, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29024866/diclofenac-but-not-celecoxib-improves-endothelial-function-in-rheumatoid-arthritis-a-study-in-adjuvant-induced-arthritis
#12
Frank Verhoeven, Perle Totoson, Christine Marie, Anne Prigent-Tessier, Daniel Wendling, Maude Tournier-Nappey, Clément Prati, Céline Demougeot
BACKGROUND AND AIMS: We aimed at investigating the effect of celecoxib (COX-2 selective inhibitor) and diclofenac (non-selective COX inhibitor) on endothelial function, and at identifying the underlying mechanisms in adjuvant-induced arthritis (AIA). METHODS: At the first signs of AIA, diclofenac (5 mg/kg twice a day, i.p), celecoxib (3 mg/kg/day, i.p) or saline (Vehicle) was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of NOS, arginase, EDHF and superoxide anions (O2(-°)) production...
November 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28978491/complement-receptor-3-mediates-nadph-oxidase-activation-and-dopaminergic-neurodegeneration-through-a-src-erk-dependent-pathway
#13
Liyan Hou, Ke Wang, Cong Zhang, Fuqiang Sun, Yuning Che, Xiulan Zhao, Dan Zhang, Huihua Li, Qingshan Wang
Microglial NADPH oxidase (Nox2) plays a key role in chronic neuroinflammation and related dopaminergic neurodegeneration in Parkinson's disease (PD). However, the mechanisms behind Nox2 activation remain unclear. Here, we revealed the critical role of complement receptor 3 (CR3), a microglia-specific pattern recognition receptor, in Nox2 activation and subsequent dopaminergic neurodegeneration by using paraquat and maneb-induced PD model. Suppression or genetic deletion of CR3 impeded paraquat and maneb-induced activation of microglial Nox2, which was associated with attenuation of dopaminergic neurodegeneration...
September 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28949377/structure-activity-relationship-of-three-synthesized-benzimidazole-based-oligosaccharides-in-human-platelet-activation
#14
Yi Chang, Wen-Hsien Hsu, Wen-Bin Yang, Thanasekaran Jayakumar, Tzu-Yin Lee, Joen-Rong Sheu, Wan-Jung Lu, Jiun-Yi Li
Antiplatelet agents have considerable benefits in the treatment of thromboembolic diseases; however, these agents still have substantial limitations due to their severe side-effects. In this study, the antiplatelet activity of three newly synthesized saccharide based benzimidazole derivatives, M3BIM, Malto-BIM and Melibio-BIM, in collagen and thrombin-stimulated human platelets in vitro was examined. Among the compounds tested, only compound M3BIM exerted concentration (20-60 µM)-dependent inhibitory effects against collagen (1 µg/ml) and thrombin (0...
September 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28941186/three-novel-mutations-in-cyba-among-22-iranians-with-chronic-granulomatous-disease
#15
M Badalzadeh, S Tajik, M R Fazlollahi, M Houshmand, F Fattahi, Z Alizadeh, M Movahedi, Z Adab, G T Khotaei, A A Hamidieh, H Heidarnazhad, Z Pourpak
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. The enzyme is at least composed of membrane-bound subunits gp91-phox and p22-phox (also named cytochrome b558 ), and cytosolic ones p40-phox, p47-phox and p67-phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22-phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive-CGD (AR-CGD) were identified...
September 20, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28939422/suppressed-ubiquitination-of-nrf2-by-p47-phox-contributes-to-nrf2-activation
#16
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/28939294/the-novel-compound-mp407-inhibits-platelet-aggregation-through-cyclic-amp-dependent-processes
#17
Chung-Shuen Lin, Tso-Hsiao Chen, I-Hsin Lin, An-Rong Lee, Tz-Chong Chou
Platelet hyperactivity plays a critical role for initiating several vascular diseases such as atherothrombosis. Therefore, development of effective antiplatelet agents is necessary for ameliorating platelet-related diseases. In this study, we investigated the effects of the new synthesized compound, MP407 on platelet aggregation and further elucidated the underlying mechanisms. Our results demonstrated that MP407 dose-dependently inhibited collagen-induced platelet aggregation, thromboxane B2 (TXB2) production, intracellular Ca(2+) mobilization, platelet membrane GPIIb/IIIa expression, and the phosphorylation of Akt, GSK3β, p38MAPK, and phospho (Ser) PKC substrate (p47)...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28916473/down-regulation-of-nox2-activity-in-phagocytes-mediated-by-atm-kinase-dependent-phosphorylation
#18
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...
December 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28878675/inhibition-of-collagen-induced-platelet-aggregation-by-the-secobutanolide-secolincomolide-a-from-lindera-obtusiloba-blume
#19
Sang-Hyuk Jung, Joo-Hui Han, Hyun-Soo Park, Jung-Jin Lee, Seo Young Yang, Young Ho Kim, Kyung-Sun Heo, Chang-Seon Myung
Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28878301/epa-dha-6-1-prevents-angiotensin-ii-induced-hypertension-and-endothelial-dysfunction-in-rats-role-of-nadph-oxidase-and-cox-derived-oxidative-stress
#20
Zahid Rasul Niazi, Grazielle C Silva, Thais Porto Ribeiro, Antonio J León-González, Mohamad Kassem, Abdur Mirajkar, Azhar Alvi, Malak Abbas, Faraj Zgheel, Valérie B Schini-Kerth, Cyril Auger
Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg(-1) per day) before chronic infusion of Ang II (0...
September 7, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
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