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https://www.readbyqxmd.com/read/27753901/os-02-01-role-of-aldosterone-and-nadph-oxidase-1-in-hypertension-associated-vascular-aging
#1
Adam P Harvey, Augusto Montezano, Khai C Wong, Katie Y Hood, Rheure Alves-Lopes, Graziela S Ceravolo, Chihiro Yabe-Nishimura, Delyth Graham, Rhian M Touyz
OBJECTIVE: In hypertension, the vasculature undergoes alterations that resemble those seen in aging. The involvement of aldosterone and Noxs in the mechanisms underlying age-associated vascular damage is unclear. We postulated that aging-like changes in the vasculature is amplified in hypertension due to increased aldosterone-induced Nox-redox signalling. DESIGN AND METHOD: We assessed vascular aging in arteries from adult WKY (18 weeks), aged WKY (52 weeks) and adult stroke-prone spontaneously hypertensive (SHRSP) rats...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27743884/peptide-screen-identifies-a-new-nadph-oxidase-inhibitor-impact-on-cell-migration-and-invasion
#2
Mohamed Mousslim, Alessandra Pagano, Nicolas Andreotti, Françoise Garrouste, Sylvie Thuault, Vincent Peyrot, Fabrice Parat, José Luis, Marcel Culcasi, Sophie Thétiot-Laurent, Sylvia Pietri, Jean-Marc Sabatier, Hervé Kovacic
The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation...
October 12, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27643247/os-02-01-role-of-aldosterone-and-nadph-oxidase-1-in-hypertension-associated-vascular-aging
#3
Adam P Harvey, Augusto Montezano, Khai C Wong, Katie Y Hood, Rheure Alves-Lopes, Graziela S Ceravolo, Chihiro Yabe-Nishimura, Delyth Graham, Rhian M Touyz
OBJECTIVE: In hypertension, the vasculature undergoes alterations that resemble those seen in aging. The involvement of aldosterone and Noxs in the mechanisms underlying age-associated vascular damage is unclear. We postulated that aging-like changes in the vasculature is amplified in hypertension due to increased aldosterone-induced Nox-redox signalling. DESIGN AND METHOD: We assessed vascular aging in arteries from adult WKY (18 weeks), aged WKY (52 weeks) and adult stroke-prone spontaneously hypertensive (SHRSP) rats...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27094494/peroxiredoxin-6-prdx6-supports-nadph-oxidase1-nox1-based-superoxide-generation-and-cell-migration
#4
Jaeyul Kwon, Aibing Wang, Devin J Burke, Howard E Boudreau, Kristen J Lekstrom, Agnieszka Korzeniowska, Ryuichi Sugamata, Yong-Soo Kim, Liang Yi, Ilker Ersoy, Stefan Jaeger, Kannappan Palaniappan, Daniel R Ambruso, Sharon H Jackson, Thomas L Leto
Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R...
July 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26781991/nadph-oxidase-1-activity-and-ros-generation-are-regulated-by-grb2-cbl-mediated-proteasomal-degradation-of-noxo1-in-colon-cancer-cells
#5
Jung Hee Joo, Hyunjin Oh, Myungjin Kim, Eun Jung An, Rae-Kwon Kim, So-Young Lee, Dong Hoon Kang, Sang Won Kang, Cheol Keun Park, Hoguen Kim, Su-Jae Lee, Daekee Lee, Jae Hong Seol, Yun Soo Bae
The generation of reactive oxygen species (ROS) is required for proper cell signaling, but must be tightly regulated to minimize deleterious oxidizing effects. Activation of the NADPH oxidases (Nox) triggers ROS production and, thus, regulatory mechanisms exist to properly control Nox activity. In this study, we report a novel mechanism in which Nox1 activity is regulated through the proteasomal degradation of Nox organizer 1 (NoxO1). We found that through the interaction between NoxO1 and growth receptor-bound protein 2 (Grb2), the Casitas B-lineage lymphoma (Cbl) E3 ligase was recruited, leading to decreased NoxO1 stability and a subsequent reduction in ROS generation upon epidermal growth factor (EGF) stimulation...
February 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/26603975/immunohistochemical-localization-of-nox-in-mouse-circumvallate-papillae
#6
Yoshiaki Kashiwabara, Kimiharu Ambe, Toshihiro Nakagawa, Hiroki Watanabe
Recently it has been reported that reactive oxygen species plays an important role in several physiological processes. Reactive oxygen species are generated by reactive oxygen-synthesizing enzymes (Nox). We immunohistochemically investigated expression and localization of the Nox family in a mouse circumvallate papillae. In the epithelium of the circumvallate papilla, Nox 1, 2, 3, and 4, Noxo1, and Noxa1 were expressed. In the circumvallate papilla, Nox2 was more weakly expressed in the lateral than in the upper part, and Nox3 was not expressed...
December 2015: Tissue & Cell
https://www.readbyqxmd.com/read/25228390/phosphorylation-of-nox1-regulates-association-with-noxa1-activation-domain
#7
Jennifer Streeter, Brandon M Schickling, Shuxia Jiang, Bojana Stanic, William H Thiel, Lokesh Gakhar, Jon C D Houtman, Francis J Miller
RATIONALE: Activation of Nox1 initiates redox-dependent signaling events crucial in the pathogenesis of vascular disease. Selective targeting of Nox1 is an attractive potential therapy, but requires a better understanding of the molecular modifications controlling its activation. OBJECTIVE: To determine whether posttranslational modifications of Nox1 regulate its activity in vascular cells. METHODS AND RESULTS: We first found evidence that Nox1 is phosphorylated in multiple models of vascular disease...
November 7, 2014: Circulation Research
https://www.readbyqxmd.com/read/25152242/immunohistochemical-localization-of-nox1-nox4-and-mn-sod-in-mouse-femur-during-endochondral-ossification
#8
Kimiharu Ambe, Hiroki Watanabe, Shinya Takahashi, Toshihiro Nakagawa
Enzymes synthesizing reactive oxygen (Nox family) have recently been identified. Elucidation of the production mechanism has been initiated, and the involvement of reactive oxygen in metabolism, intracellular transport, signal transmission and apoptosis has been reported. We immunohistochemically investigated expression and localization of the Nox family in endochondral ossification using a normal mouse femur. Weakly positive reactions with Nox1, Noxa1, and Noxo1 were observed in the zones of proliferative and prehypertrophic chondrocytes at 3 weeks of age...
December 2014: Tissue & Cell
https://www.readbyqxmd.com/read/25137373/functional-networks-of-nucleocytoplasmic-transport-related-genes-differentiate-ischemic-and-dilated-cardiomyopathies-a-new-therapeutic-opportunity
#9
María Micaela Molina-Navarro, Juan Carlos Triviño, Luis Martínez-Dolz, Francisca Lago, Jose Ramón González-Juanatey, Manuel Portolés, Miguel Rivera
Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA...
2014: PloS One
https://www.readbyqxmd.com/read/25062272/nox4-a-hydrogen-peroxide-generating-oxygen-sensor
#10
Yukio Nisimoto, Becky A Diebold, Daniela Cosentino-Gomes, Daniela Constentino-Gomes, J David Lambeth
Nox4 is an oddity among members of the Nox family of NADPH oxidases [seven isoenzymes that generate reactive oxygen species (ROS) from molecular oxygen] in that it is constitutively active. All other Nox enzymes except for Nox4 require upstream activators, either calcium or organizer/activator subunits (p47(phox), NOXO1/p67(phox), and NOXA1). Nox4 may also be unusual as it reportedly releases hydrogen peroxide (H₂O₂) in contrast to Nox1-Nox3 and Nox5, which release superoxide, although this result is controversial in part because of possible membrane compartmentalization of superoxide, which may prevent detection...
August 12, 2014: Biochemistry
https://www.readbyqxmd.com/read/24792722/nox1-activation-by-%C3%AE-pix-and-the-role-of-ser-340-phosphorylation
#11
Yuuki Kaito, Ryosuke Kataoka, Kento Takechi, Tatsuya Mihara, Minoru Tamura
Rac is an activating factor for Nox1, an O2(-)-generating NADPH oxidase, expressed in the colon and other tissues. Rac requires a GDP-GTP exchange factor for activation. Nox1 activation by βPix has been demonstrated in cell lines. We examined the effects of βPix and its phosphomimetic mutant on endogenous Nox1 in Caco-2 cells transfected with Noxo1 and Noxa1. βPix expression enhanced O2(-) production in resting cells and cells stimulated with EGF or phorbol ester. βPix(S340E) further enhanced O2(-) production, while βPix(S340A) eliminated the βPix effect...
May 29, 2014: FEBS Letters
https://www.readbyqxmd.com/read/24334207/the-role-of-nadph-oxidase-in-a-mouse-model-of-fetal-alcohol-syndrome
#12
Alexandria J Hill, Nathan Drever, Huaizhi Yin, Esther Tamayo, George Saade, Egle Bytautiene
OBJECTIVE: Fetal alcohol syndrome (FAS) is the most common cause of nongenetic mental retardation. Oxidative stress is one of the purported mechanisms. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is an enzyme involved in the production of reactive oxygen species. Our objective was to evaluate NOX in the fetal brain of a well-validated mouse model of FAS. STUDY DESIGN: Timed, pregnant C57BL/6J mice were injected intraperitoneally with 0.03 mL/g of either 25% ethyl alcohol or saline...
May 2014: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/24316858/expression-of-oxidative-stress-and-antioxidant-defense-genes-in-the-kidney-of-inbred-mice-after-intestinal-ischemia-and-reperfusion
#13
Roberto Teruya, Adauto Tsutomu Ikejiri, Frederico Somaio Neto, José Carlos Chaves, Paulo Roberto Bertoletto, Murched Omar Taha, Djalma José Fagundes
PURPOSE: To determine the gene expressions profile related to the oxidative stress and the antioxidant response in the kidneys of mice subjected to intestinal ischemia and reperfusion. METHODS: Twelve inbred mice (C57BL/6) were randomly assigned to one of two groups: the control group (CG) underwent anesthesia and was observed for 120 min and the ischemia/reperfusion group (IRG), animals were anesthetized and subjected to laparotomy and ischemia for 60 minutes followed by 60 minutes of reperfusion...
December 2013: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/24187133/selective-recapitulation-of-conserved-and-nonconserved-regions-of-putative-noxa1-protein-activation-domain-confers-isoform-specific-inhibition-of-nox1-oxidase-and-attenuation-of-endothelial-cell-migration
#14
Daniel J Ranayhossaini, Andres I Rodriguez, Sanghamitra Sahoo, Beibei B Chen, Rama K Mallampalli, Eric E Kelley, Gabor Csanyi, Mark T Gladwin, Guillermo Romero, Patrick J Pagano
Excessive vascular and colon epithelial reactive oxygen species production by NADPH oxidase isoform 1 (Nox1) has been implicated in a number of disease states, including hypertension, atherosclerosis, and neoplasia. A peptide that mimics a putative activation domain of the Nox1 activator subunit NOXA1 (NOXA1 docking sequence, also known as NoxA1ds) potently inhibited Nox1-derived superoxide anion (O2·-) production in a reconstituted Nox1 cell-free system, with no effect on Nox2-, Nox4-, Nox5-, or xanthine oxidase-derived reactive oxygen species production as measured by cytochrome c reduction, Amplex Red fluorescence, and electron paramagnetic resonance...
December 20, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24008014/c-terminal-truncation-of-noxa1-greatly-enhances-its-ability-to-activate-nox2-in-a-pure-reconstitution-system
#15
Masahito Kawano, Rey Ishii, Yuki Yoshioka, Takehito Fukuda, Minoru Tamura
Noxa1 activates Nox2 together with Noxo1 and Rac in a pure reconstitution system, but the resulting activity is considerably lower than that induced by p67(phox) and p47(phox). In this study, we found that C-terminal-truncated forms of Noxa1 exhibited higher activities than full-length Noxa1. Of the truncations examined, Noxa1(1-225) showed the highest ability for activation. Kinetic studies revealed that Noxa1(1-225) had a threefold higher Vmax value than full-length Noxa1 with a similar EC50 value. The affinities of Noxo1 and RacQ61L were not much altered by the truncation...
October 15, 2013: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/23957209/phosphorylation-of-noxo1-at-threonine-341-regulates-its-interaction-with-noxa1-and-the-superoxide-producing-activity-of-nox1
#16
Asataro Yamamoto, Ryu Takeya, Masaki Matsumoto, Keiichi I Nakayama, Hideki Sumimoto
UNLABELLED: Superoxide production by Nox1, a member of the Nox family NAPDH oxidases, requires expression of its regulatory soluble proteins Noxo1 (Nox organizer 1) and Noxa1 (Nox activator 1) and is markedly enhanced upon cell stimulation with phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC). The mechanism underlying PMA-induced enhancement of Nox1 activity, however, remains to be elucidated. Here we show that, in response to PMA, Noxo1 undergoes phosphorylation at multiple sites, which is inhibited by the PKC inhibitor GF109203X...
October 2013: FEBS Journal
https://www.readbyqxmd.com/read/23551967/a-combined-blood-based-gene-expression-and-plasma-protein-abundance-signature-for-diagnosis-of-epithelial-ovarian-cancer-a-study-of-the-ovcad-consortium
#17
Dietmar Pils, Dan Tong, Gudrun Hager, Eva Obermayr, Stefanie Aust, Georg Heinze, Maria Kohl, Eva Schuster, Andrea Wolf, Jalid Sehouli, Ioana Braicu, Ignace Vergote, Toon Van Gorp, Sven Mahner, Nicole Concin, Paul Speiser, Robert Zeillinger
BACKGROUND: The immune system is a key player in fighting cancer. Thus, we sought to identify a molecular 'immune response signature' indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC. METHODS: Comparing the expression of 32,000 genes in a leukocytes fraction from 44 EOC patients and 19 controls, three uncorrelated shrunken centroid models were selected, comprised of 7, 14, and 6 genes...
2013: BMC Cancer
https://www.readbyqxmd.com/read/23322165/noxo1-phosphorylation-on-serine-154-is-critical-for-optimal-nadph-oxidase-1-assembly-and-activation
#18
Maya Debbabi, Yolande Kroviarski, Odile Bournier, Marie-Anne Gougerot-Pocidalo, Jamel El-Benna, Pham My-Chan Dang
Reactive oxygen species (ROS) production by NADPH oxidase 1 (NOX1), which is mainly expressed in colon epithelial cells, requires the membrane-bound component p22(PHOX) and the cytosolic partners NOX organizer 1 (NOXO1), NOX activator 1 (NOXA1), and Rac1. Contrary to that of its phagocyte counterpart NOX2, the molecular basis of NOX1 regulation is not clear. Because NOXO1 lacks the phosphorylated region found in its homolog p47(PHOX), the current view is that NOX1 activation occurs without NOXO1 phosphorylation...
April 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/22467573/neuronal-nad-p-h-oxidases-contribute-to-ros-production-and-mediate-rgc-death-after-ischemia
#19
Galina Dvoriantchikova, Jeff Grant, Andrea Rachelle C Santos, Eleut Hernandez, Dmitry Ivanov
PURPOSE: To study the role of neuronal nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase-dependent reactive oxygen species (ROS) production in retinal ganglion cell (RGC) death after ischemia. METHODS: Ischemic injury was induced by unilateral elevation of intraocular pressure via direct corneal cannulation. For in vitro experiments, RGCs isolated by immunopanning from retinas were exposed to oxygen and glucose deprivation (OGD). The expression levels of NAD(P)H oxidase subunits were evaluated by quantitative PCR, immunocytochemistry, and immunohistochemistry...
May 2012: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/22342885/the-noxo1%C3%AE-px-domain-preferentially-targets-ptdins-4-5-p2-and-ptdins-3-4-5-p3
#20
Nicole Y Davis, Linda C McPhail, David A Horita
NOXO1β [NOXO1 (Nox organizer 1) β] is a cytosolic protein that, in conjunction with NOXA1 (Nox activator 1), regulates generation of reactive oxygen species by the NADPH oxidase 1 (Nox1) enzyme complex. NOXO1β is targeted to membranes through an N-terminal PX (phox homology) domain. We have used NMR spectroscopy to solve the structure of the NOXO1β PX domain and surface plasmon resonance (SPR) to assess phospholipid specificity. The solution structure of the NOXO1β PX domain shows greatest similarity to that of the phosphatidylinositol 3-kinase-C2α PX domain with regard to the positions and types of residues that are predicted to interact with phosphatidylinositol phosphate (PtdInsP) head groups...
April 13, 2012: Journal of Molecular Biology
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