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NOX4

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https://www.readbyqxmd.com/read/28099519/crispr-cas9-mediated-nox4-knockout-inhibits-cell-proliferation-and-invasion-in-hela-cells
#1
Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J Morris, Junsoo Park, Cai Huang
Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#2
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28088644/tert-butyl-hydroperoxide-t-bhp-induced-apoptosis-and-necroptosis-in-endothelial-cells-roles-of-nox4-and-mitochondrion
#3
Wenwen Zhao, Haitao Feng, Wen Sun, Kang Liu, Jin-Jian Lu, Xiuping Chen
Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) of t-BHP (t-BHPL) and high concentration (500μM) of t-BHP (t-BHPH). Both t-BHPL and t-BHPH induced endothelial cell death was determined. T-BHPL induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHPL-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so...
January 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28087886/d-chiro-inositol-ameliorates-endothelial-dysfunction-via-inhibition-of-oxidative-stress-and-mitochondrial-fission
#4
Bobo Zhang, Xudan Guo, Yunlong Li, Qiang Peng, Jinfeng Gao, Baolin Liu, Min Wang
SCOPE: D-chiro inositol (DCI), an isomer of inositol, possesses anti-oxidative and endothelial protective properties. The mechanism by which DCI prevents endothelial dysfunction was investigated, with emphasis on oxidative stress. METHODS AND RESULTS: DCI was found to inhibit NOX4 induction and enhance Nrf2 activity in palmitate (PA)-stimulated cells, showing that DCI prevents oxidative stress. DCI suppressed Ser616 phosphorylation and increased Ser637 phosphorylation of Drp1 and inhibited PA-induced mitochondrial fission...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28081539/regulation-of-anoikis-resistance-by-nadph-oxidase-4-and-epidermal-growth-factor-receptor
#5
Hyeryeong Kim, Jee Young Sung, Eun-Kyung Park, Seongho Kho, Kyung Hee Koo, Seog-Yun Park, Sung-Ho Goh, Yoon Kyung Jeon, Sekyung Oh, Byung-Kiu Park, Yong-Keun Jung, Yong-Nyun Kim
BACKGROUND: Normal cells are sensitive to anoikis, which is a cell detachment-induced apoptosis. However, cancer cells acquire anoikis resistance that is essential for successful metastasis. This study aimed to demonstrate the function and potential mechanism of NADPH oxidase 4 (NOX4) and EGFR activation in regulating anoikis resistance in lung cancer. METHODS: Cells were cultured either in the attached or suspended condition. Cell viability was measured by cell counting and live and dead cell staining...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28078487/the-role-of-the-nox4-derived-ros-mediated-rhoa-rho-kinase-pathway-in-rat-hypertension-induced-by-chronic-intermittent-hypoxia
#6
Wen Lu, Jing Kang, Ke Hu, Si Tang, Xiufang Zhou, Lifang Xu, Yuanyuan Li, Shuhui Yu
BACKGROUND: Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke...
January 11, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28074262/activated-microglia-induce-the-production-of-reactive-oxygen-species-and-promote-apoptosis-of-co-cultured-retinal-microvascular-pericytes
#7
Xinyi Ding, Meng Zhang, Ruiping Gu, Gezhi Xu, Haixiang Wu
PURPOSE: Pericyte apoptosis is a predominant feature of early diabetic retinopathy. In diabetic retinopathy, activated microglia migrate and release proinflammatory cytokines that contribute to disruption of the blood-retinal barrier, neuronal loss, and enhanced ROS production. Reactive oxygen species (ROS) are implicated in pericyte death; however, the mechanism by which activated microglia affect retinal microvascular pericytes is unclear. We hypothesized that activated microglia may promote pericyte apoptosis by enhancing ROS production...
January 10, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28063949/vitamin-d-supplementation-inhibits-oxidative-stress-and-upregulate-sirt1-ampk-glut4-cascade-in-high-glucose-treated-3t3l1-adipocytes-and-in-adipose-tissue-of-high-fat-diet-fed-diabetic-mice
#8
Prasenjit Manna, Arunkumar E Achari, Sushil K Jain
This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0-50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells...
January 4, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28063381/brd4-inhibition-attenuates-unilateral-ureteral-obstruction-induced-fibrosis-by-blocking-tgf-%C3%AE-mediated-nox4-expression
#9
Baoshang Zhou, Jiao Mu, Yi Gong, Caibao Lu, Youguang Zhao, Ting He, Zhexue Qin
Uncovering new therapeutic targets for renal fibrosis holds promise for the treatment of chronic kidney diseases. Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively ameliorate pathological fibrotic responses. However, the pharmacological effects and underlying mechanisms of these inhibitors in renal fibrosis remain elusive. In this study, we determined that the inhibition of Brd4, a BET family member, with a selective potent chemical inhibitor, JQ1, could prevent the development of renal fibrosis and block the progression of fibrosis in rats that have undergone unilateral ureteral obstruction (UUO)...
December 30, 2016: Redox Biology
https://www.readbyqxmd.com/read/28063379/oxidative-stress-mitochondrial-abnormalities-and-antioxidant-defense-in-ataxia-telangiectasia-bloom-syndrome-and-nijmegen-breakage-syndrome
#10
REVIEW
Mateusz Maciejczyk, Bozena Mikoluc, Barbara Pietrucha, Edyta Heropolitanska-Pliszka, Malgorzata Pac, Radosław Motkowski, Halina Car
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis...
December 28, 2016: Redox Biology
https://www.readbyqxmd.com/read/28062507/brown-adipose-tissue-regulates-small-artery-function-through-nadph-oxidase-4-derived-hydrogen-peroxide-and-redox-sensitive-protein-kinase-g-1%C3%AE
#11
Malou Friederich-Persson, Aurelie Nguyen Dinh Cat, Patrik Persson, Augusto C Montezano, Rhian M Touyz
OBJECTIVE: Biomedical interest in brown adipose tissue (BAT) has increased since the discovery of functionally active BAT in adult humans. Although white adipose tissue (WAT) influences vascular function, vascular effects of BAT are elusive. Thus, we investigated the regulatory role and putative vasoprotective effects of BAT, focusing on hydrogen peroxide, nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), and redox-sensitive signaling. APPROACH AND RESULTS: Vascular reactivity was assessed in wild-type and Nox4-knockout mice (Nox4(-/-)) by wire myography in the absence and presence of perivascular adipose tissue of different phenotypes from various adipose depots: (1) mixed WAT/BAT (inguinal adipose tissue) and (2) WAT (epididymal visceral fat) and BAT (intrascapular fat)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062496/adipocyte-specific-deficiency-of-nadph-oxidase-4-delays-the-onset-of-insulin-resistance-and-attenuates-adipose-tissue-inflammation-in-obesity
#12
Laura J Den Hartigh, Mohamed Omer, Leela Goodspeed, Shari Wang, Tomasz Wietecha, Kevin D O'Brien, Chang Yeop Han
OBJECTIVE: Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062482/dysregulated-nox4-ubiquitination-contributes-to-redox-imbalance-and-age-related-severity-of-acute-lung-injury
#13
Sunmi Palumbo, Yoon-Joo Shin, Kareem Ahmad, Ankit A Desai, Hector Quijada, Mohamed Mohamed, Adam Knox, Saad Sammani, Brett A Colson, Ting Wang, Joe G N Garcia, Louise Hecker
Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population(higher incidence and mortality). The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 months) and aged (18 months) mice using a two-hit pre-clinical model. Compared to young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx, levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28057038/aldose-reductase-mediates-endothelial-cell-dysfunction-induced-by-high-uric-acid-concentrations
#14
Zhiyong Huang, Quan Hong, Xueguang Zhang, Wenzhen Xiao, Liyuan Wang, Shaoyuan Cui, Zhe Feng, Yang Lv, Guangyan Cai, Xiangmei Chen, Di Wu
BACKGROUND: Uric acid (UA) is an antioxidant found in human serum. However, high UA levels may also have pro-oxidant functions. According to previous research, aldose reductase (AR) plays a vital role in the oxidative stress-related complications of diabetes. We sought to determine the mechanism by which UA becomes deleterious at high concentrations as well as the effect of AR in this process. METHOD: Endothelial cells were divided into three groups cultured without UA or with 300 μM or 600 μM UA...
January 5, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28053285/protective-effect-of-tanshinone-iia-against-cardiac-hypertrophy-in-spontaneously-hypertensive-rats-through-inhibiting-the-cys-c-wnt-signaling-pathway
#15
Jun Feng, Hua-Wen Chen, Li-Juan Pi, Jin Wang, Da-Qian Zhan
The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049732/nadph-oxidase-4-nox4-suppresses-mitochondrial-biogenesis-and-bioenergetics-in-lung-fibroblasts-via-a-nuclear-factor-erythroid-derived-2-like-2-nrf2-dependent-pathway
#16
Karen Bernard, Naomi J Logsdon, Veronica Miguel, Gloria A Benavides, Jianhua Zhang, A Brent Carter, Victor M Darley-Usmar, Victor J Thannickal
Mitochondrial bioenergetics are critical for cellular homeostasis and stress responses. The reactive oxygen species (ROS)-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, host defense and tissue fibrosis. In this study, we explored the role of constitutive Nox4 activity in regulating mitochondrial function. An increase in mitochondrial oxygen consumption and reserve capacity was observed in murine and human lung fibroblasts with genetic deficiency (or silencing) of Nox4...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28039839/lps-induced-renal-inflammation-is-prevented-by-epicatechin-in-rats
#17
Paula Denise Prince, Laura Fischerman, Jorge E Toblli, Cesar G Fraga, Monica Galleano
This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by LPS administration in rats. Male Sprague Dawley rats were fed for 4 days a diet without or with supplementation with (-)-epicatechin (80mg/kg BW/d), and subsequently i.p. injected with lipopolysaccharide (LPS). Six hours after injection, LPS-treated rats exhibited increased plasma creatinine and urea levels as indicators of impaired renal function. The renal cortex of the LPS-treated rats showed: i) increased expression of inflammatory molecules (TNF-α, iNOS and IL-6); ii) activation of several steps of NF-κB pathway; iii) overexpression of TLR4, and iv) higher superoxide anion production and lipid peroxidation index in association with increased levels of gp91(phox) and p47(phox) (NOX2) and NOX4...
December 22, 2016: Redox Biology
https://www.readbyqxmd.com/read/28038425/knock-out-of-the-nadph-oxidase-nox4-has-no-impact-on-life-span-in-mice
#18
Flavia Rezende, Christoph Schürmann, Susanne Schütz, Sabine Harenkamp, Eva Herrmann, Michael Seimetz, Norbert Weißmann, Katrin Schröder
The free radical theory of aging suggests reactive oxygen species as a main reason for accumulation of damage events eventually leading to aging. Nox4, a member of the family of NADPH oxidases constitutively produces ROS and therefore has the potential to be a main driver of aging. Herein we analyzed the life span of Nox4 deficient mice and found no difference when compared to their wildtype littermates. Accordingly neither Tert expression nor telomere length was different in cells isolated from those animals...
December 22, 2016: Redox Biology
https://www.readbyqxmd.com/read/28036029/fenofibrate-therapy-restores-antioxidant-protection-and-improves-myocardial-insulin-resistance-in-a-rat-model-of-metabolic-syndrome-and-myocardial-ischemia-the-role-of-angiotensin-ii
#19
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28035366/inhibitory-effects-of-alpha-lipoic-acid-on-oxidative-stress-in-the-rostral-ventrolateral-medulla-in-rats-with-salt-induced-hypertension
#20
Yu-Peng Huang, Hong-Yan Jin, Hui-Ping Yu
Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alpha‑lipoic acid (ALA) is widely recognized for its potent superoxide inhibitory properties, and it can safely penetrate deep into the brain. The aim of this study was to explore whether ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the NAD(P)H oxidase (NOX)-derived overproduction of reactive oxygen species (ROS) in the mitochondria in the RVLM, and thus attenuating the development of salt‑induced hypertension...
February 2017: International Journal of Molecular Medicine
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