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https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#1
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28431936/galectin-3-mediates-the-pulmonary-arterial-hypertension-induced-right-ventricular-remodeling-through-interacting-with-nadph-oxidase-4
#2
Jingni He, Xiaohui Li, Hui Luo, Tangzhiming Li, Lin Zhao, Qiangqiang Qi, Yuwei Liu, Zaixin Yu
Pulmonary arterial hypertension (PAH) is a progressive disorder that affects both pulmonary vasculature and the heart. The response of the right ventricle (RV) to the increased afterload is an important determinant of the PAH final outcome. Galectin-3 (Gal-3), a novel biomarker in left cardiac remodeling, takes part in multiple pathophysiological processes including the inflammation, fibrosis, immunity, and oxidative stress. The levels of Gal-3 are elevated in PAH patients, although the exact mechanisms underlie the PAH-induced right ventricular structural changes remain unclear...
March 27, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28430866/maternal-high-sucrose-diets-altered-vascular-large-conductance-ca2-activated-k-channels-via-reactive-oxygen-species-in-offspring-rats%C3%A2
#3
Xueqin Feng, Xiuwen Zhou, Wenna Zhang, Xiang Li, Axin He, Bailin Liu, Ruixiu Shi, Lei Wu, Jue Wu, Di Zhu, Na Li, Miao Sun, Zhice Xu
Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high-sucrose (HS). We found that prenatal high-sucrose diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28424170/ros-induced-ros-release-orchestrated-by-nox4-nox2-and-mitochondria-in-vegf-signaling-and-angiogenesis
#4
Young-Mee Kim, Seok-Jo Kim, Ryosuke Tatsunami, Hisao Yamamura, Tohru Fukai, Masuko Ushio-Fukai
Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min...
April 19, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28423654/mcl-1-regulates-reactive-oxygen-species-via-nox4-during-chemotherapy-induced-senescence
#5
Abeba Demelash, Lukas W Pfannenstiel, Li Liu, Brian R Gastman
Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422720/overexpression-of-nox4-predicts-poor-prognosis-and-promotes-tumor-progression-in-human-colorectal-cancer
#6
Xiao-Lu Lin, Li Yang, Seng-Wang Fu, Wen-Feng Lin, Yun-Jie Gao, Hao-Yan Chen, Zhi-Zheng Ge
NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS) production, has been increasingly reported to be involved in tumorigenesis and/or tumor progression, but limited data are available regarding the role of NOX4 in colorectal carcinoma (CRC). We retrieved six independent investigations from Oncomine database and found that NOX4 is highly expressed in CRC tissues compared with corresponding normal controls. Similar results were also found in clinical specimens at both mRNA and protein levels...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396118/superoxide-and-hydrogen-peroxide-counterregulate-myogenic-contractions-in-renal-afferent-arterioles-from-a-mouse-model-of-chronic-kidney-disease
#7
Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K Griendling, W Robert Taylor, Pedro A Jose, Anton Wellsten, William J Welch, Christopher S Wilcox
Myogenic contractions protect kidneys from barotrauma but are impaired in chronic kidney disease (CKD). Since myogenic contractions are enhanced by superoxide but impaired by hydrogen peroxide, we tested the hypothesis that they are counterregulated by superoxide and H2O2 from NOX2/p47phox and/or NOX4/POLDIP2 in CKD. Myogenic contraction in isolated perfused afferent arterioles from mice with surgical 5/6 nephrectomy or sham operations fed a 6% sodium chloride diet was measured directly while superoxide and H2O2 were measured by fluorescence microscopy...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28395989/naringin-ameliorates-diabetic-nephropathy-by-inhibiting-nadph-oxidase-4
#8
Junwei Zhang, Suxia Yang, Huicong Li, Fang Chen, Jun Shi
Naringin, a naturally flavanone glycoside, has been previously demonstrated to alleviate diabetic kidney disease by inhibiting oxidative stress and inflammatory reaction. However, the underlying mechanism of naringin in diabetic nephropathy (DN) has not been fully elucidated. Here, the beneficial effect of naringin on DN in streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes and its underlying mechanism were elaborated. The result revealed that naringin alleviated STZ-induced renal dysfunction and injury in DN rats, relieved STZ-induced oxidative stress in vivo and inhibited HG-induced apoptosis and reactive oxygen species level i20n vitro...
June 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28389561/tgf-beta-1-induced-cd44v6-nox4-signaling-in-pathogenesis-of-idiopathic-pulmonary-fibrosis
#9
Shibnath Ghatak, Vincent C Hascall, Roger R Markwald, Carol Feghali-Bostwick, Carol M Artlett, Monika Gooz, Galina S Bogatkevich, Ilia Atanelishvili, Richard M Silver, Jeanette Wood, Victor J Thannickal, Suniti Misra
Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblasts phenotype has prevented the development of targeted therapies for IPF. Our previous study (1) showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44v6 (CD44-variants containing exon-6), which enhances the TGF-beta-1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28386230/role-of-nadph-oxidase-4-in-human-endothelial-progenitor-cells
#10
Nora Y Hakami, Amaresh K Ranjan, Anandwardhan A Hardikar, Greg J Dusting, Hitesh M Peshavariya
Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28383062/nox4-regulates-ccr2-and-ccl2-mrna-stability-in-alcoholic-liver-disease
#11
Yu Sasaki, Ali Dehnad, Sarah Fish, Ai Sato, Joy Jiang, Jijing Tian, Kathrin Schröder, Ralf Brandes, Natalie J Török
Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28363602/zinc-regulates-nox1-expression-through-a-nf-%C3%AE%C2%BAb-and-mitochondrial-ros-dependent-mechanism-to-induce-senescence-of-vascular-smooth-muscle-cells
#12
G Salazar, J Huang, R G Feresin, Y Zhao, K K Griendling
AIMS: The role of oxidative stress and inflammation in the development and progression of cardiovascular diseases (CVD) is well established. Increases in oxidative stress can further exacerbate the inflammatory response and lead to cellular senescence. We previously reported that angiotensin II (Ang II) and zinc increase reactive oxygen species (ROS) and cause senescence of vascular smooth muscle cells (VSMCs) and that senescence induced by Ang II is a zinc-dependent process. Zinc stimulated NADPH oxidase (Nox) activity; however, the role of Nox isoforms in zinc effects was not determined...
March 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28360125/cellular-levels-of-growth-factor-receptor-bound-protein-2-grb2-and-cytoskeleton-stability-are-correlated-in-a-neurodegenerative-scenario
#13
Piyali Majumder, Kasturi Roy, Brijesh Kumar Singh, Nihar Ranjan Jana, Debashis Mukhopadhyay
Alzheimer's Disease (AD) manifests neuronal loss. On the premises of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD like conditions. Two predominant molecular features of AD, extracellular accumulation of Aβ oligomers and intracellular elevation of AICD levels, have been used to closely inspect the series of signaling events. In their presence, multiple signaling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton and Grb2 partially counterbalances the cytoskeletal loss...
March 30, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28356077/evolutionary-origin-and-function-of-nox4-art-an-arthropod-specific-nadph-oxidase
#14
Ana Caroline Paiva Gandara, André Torres, Ana Cristina Bahia, Pedro L Oliveira, Renata Schama
BACKGROUND: NADPH oxidases (NOX) are ROS producing enzymes that perform essential roles in cell physiology, including cell signaling and antimicrobial defense. This gene family is present in most eukaryotes, suggesting a common ancestor. To date, only a limited number of phylogenetic studies of metazoan NOXes have been performed, with few arthropod genes. In arthropods, only NOX5 and DUOX genes have been found and a gene called NOXm was found in mosquitoes but its origin and function has not been examined...
March 29, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28351775/nox2-nox4-and-mitochondrial-derived-reactive-oxygen-species-contribute-to-angiopoietin-1-signaling-and-angiogenic-responses-in-endothelial-cells
#15
Sharon Harel, Dominique Mayaki, Veronica Sanchez, Sabah N A Hussain
Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes survival, migration, and differentiation of endothelial cells. Several studies have linked reactive oxygen species (ROS) to Ang-1 signaling and distinct angiogenic responses, but the molecular sources of these ROS have never been clearly identified. In this study, we have identified source-specific contributions of ROS to Ang-1/Tie 2 signaling and angiogenic responses in human umbilical vein endothelial cells (HUVECs), specifically the differential contributions of mitochondrial ROS (mtROS) and ROS from two isoforms of NADPH oxidase (NOX2, NOX4)...
March 25, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28351769/quercetin-attenuates-high-fat-diet-induced-atherosclerosis-in-apolipoprotein-e-knockout-mice-a-critical-role-of-nadph-oxidase
#16
Lin Xiao, Liang Liu, Xiaoping Guo, Shanshan Zhang, Jing Wang, Feng Zhou, Liegang Liu, Yuhan Tang, Ping Yao
Reactive oxygen species (ROS) have emerged as important molecules in cardiovascular function. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in phagocytic and vascular cells. Several lines of evidence indicate that quercetin contributes to protecting against atherosclerosis. Herein, we investigated the effect of quercetin on alleviating atherosclerosis by regulating NADPH oxidase subunits expression in vivo, and explored the mechanism of quercetin suppressing the ROS overproduction stimulated by ox-LDL in mouse peritoneal macrophages (MPMs)...
March 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28347868/teneligliptin-a-dipeptidyl-peptidase-4-inhibitor-attenuated-pro-inflammatory-phenotype-of-perivascular-adipose-tissue-and-inhibited-atherogenesis-in-normoglycemic-apolipoprotein-e-deficient-mice
#17
Hotimah Masdan Salim, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Michio Shimabukuro, Masataka Sata
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0...
March 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28336812/tgf-%C3%AE-1-stimulates-hdac4-nucleus-to-cytoplasm-translocation-and-nadph-oxidase4-derived-reactive-oxygen-species-in-normal-human-lung-fibroblasts
#18
Weichao Guo, Shigeki Saito, Cecilia G Sanchez, Yan Zhuang, Rafael E Gongora Rosero, Bin Shan, Fayong Luo, Joseph A Lasky
Myofibroblasts are important mediators of fibrogenesis, thus blocking fibroblast to myofibroblast differentiation (FMD) may be an effective strategy to treat pulmonary fibrosis (PF). Previously we reported that HDAC4 activity is necessary for TGF-β1-induced human lung FMD. Here we show that TGF-β1 increases NOX4 mRNA and protein expression in normal human lung fibroblasts (NHLFs) and causes nuclear export of HDAC4. Application of the NOX family inhibitor, diphenyleneiodonium chloride (DPI), reduces TGF-β1-induced HDAC4 nuclear export, expression of the myofibroblast marker α-smooth muscle actin (α-SMA), and α-SMA fiber formation...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28335679/puerarin-attenuates-renal-fibrosis-by-reducing-oxidative-stress-induced-epithelial-cell-apoptosis-via-mapk-signal-pathways-in-vivo-and-in-vitro
#19
Xiangjun Zhou, Chen Bai, Xinbo Sun, Xiaoxin Gong, Yong Yang, Congbo Chen, Guang Shan, Qisheng Yao
Puerarin (PR) is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been widely used in traditional Chinese herbal medicine for the treatment of various diseases. Oxidative stress and epithelial cell apoptosis play important roles in the renal fibrotic process. The present study aimed to determine whether or not PR inhibits renal fibrosis by reducing oxidative stress induced-epithelial cell apoptosis. In vivo, unilateral ureteral obstruction (UUO) induced renal fibrosis, and epithelial cell apoptosis...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28330417/involvement-of-nox2-and-nox4-nadph-oxidases-in-early-brain-injury-after-subarachnoid-hemorrhage
#20
Li Zhang, Zhen Li, Dongxia Feng, Haitao Shen, Xiaodi Tian, Haiying Li, Zhong Wang, Gang Chen
Oxidative stress is responsible for a poor prognosis of subarachnoid hemorrhage (SAH) patients. Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in central nervous system (CNS). Here, we investigated the role of Nox4 and whether there was a synergistic effect of Nox2 and Nox4 in SAH-induced EBI. Clinical brain biopsies of four patients with traumatic brain injury (TBI) and perihematomal brain tissue from six subjects with SAH were examined...
April 9, 2017: Free Radical Research
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