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nox4 kidney

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
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
Li Gao, Wei-Feng Wu, Lei Dong, Gui-Ling Ren, Hai-Di Li, Qin Yang, Xiao-Feng Li, Tao Xu, Zeng Li, Bao-Ming Wu, Tao-Tao Ma, Cheng Huang, Yan Huang, Lei Zhang, Xiongwen Lv, Jun Li, Xiao-Ming Meng
Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy...
2016: Frontiers in Pharmacology
Hongyan Mo, Qinyu Wu, Jinhua Miao, Congwei Luo, Xue Hong, Yongping Wang, Lan Tang, Fan Fan Hou, Youhua Liu, Lili Zhou
AIMS: Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of CXCR4, the chemokine receptor for SDF-1α, in mediating oxidative stress-induced podocyte injury. RESULTS: In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by MDA assay, nitrotyrosine staining and secretion of 8-OHdG in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase...
December 13, 2016: Antioxidants & Redox Signaling
Stellor Nlandu-Khodo, Romain Dissard, Udo Hasler, Matthias Schäfer, Haymo Pircher, Pidder Jansen-Durr, Karl Heinz Krause, Pierre-Yves Martin, Sophie de Seigneux
NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI...
December 7, 2016: Scientific Reports
Karina Thieme, Karolline S Da Silva, Nelly T Fabre, Sergio Catanozi, Maria Beatriz Monteiro, Daniele Pereira Santos-Bezerra, Juliana Martins Costa-Pessoa, Maria Oliveira-Souza, Ubiratan F Machado, Marisa Passarelli, Maria Lucia Correa-Giannella
AIM: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). METHODS: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed...
2016: Cellular Physiology and Biochemistry
Rita Valenzuela, Maria A Costa-Besada, Javier Iglesias-Gonzalez, Emma Perez-Costas, Begoña Villar-Cheda, Pablo Garrido-Gil, Miguel Melendez-Ferro, Ramon Soto-Otero, Jose L Lanciego, Daniel Henrion, Rafael Franco, Jose L Labandeira-Garcia
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the 'classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2)...
October 20, 2016: Cell Death & Disease
Thiago Bruder-Nascimento, Glaucia Callera, Augusto Cesar Montezano, Tayze T Antunes, Ying He, Aurelie Nguyen Dinh Cat, Nathanne S Ferreira, Pedro A Barreto, Vânia C Olivon, Rita C Tostes, Rhian M Touyz
Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p...
2016: PloS One
Sayo Koike, Shozo Yano, Sayuri Tanaka, Abdullah M Sheikh, Atsushi Nagai, Toshitsugu Sugimoto
Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium deposition in vascular smooth muscle cells (VSMCs) through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms...
September 16, 2016: International Journal of Molecular Sciences
Lin Xiao, Jing-Hui Dong, Sheng Jin, Hong-Mei Xue, Qi Guo, Xu Teng, Yu-Ming Wu
Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats...
2016: Oxidative Medicine and Cellular Longevity
Huibin Nie, Xia Xue, Gang Liu, Guangju Guan, Haiying Liu, Lina Sun, Long Zhao, Xueling Wang, Zhixin Chen
Nitroalkene derivative of oleic acid (OA-NO2), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO2 in an in vitro model of renal ischemia/reperfusion (I/R) injury...
2016: Free Radical Research
Hye Sook Min, Jin Joo Cha, Kitae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyunwook Kim, Ji Eun Lee, Jee Young Han, Lak Shin Jeong, Dae Ryong Cha, Young Sun Kang
The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888...
September 2016: Journal of Korean Medical Science
Keith G Avin, Neal X Chen, Jason M Organ, Chad Zarse, Kalisha O'Neill, Richard G Conway, Robert J Konrad, Robert L Bacallao, Matthew R Allen, Sharon M Moe
Skeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i...
2016: PloS One
Stephanie Eid, Suzan Boutary, Kawthar Braysh, Ramzi Sabra, Charbel Massaad, Ahmed Hamdy, Awad Rashed, Sarah Moodad, Karen Block, Yves Gorin, Hanna E Abboud, Assaad Antoine Eid
AIM: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mTORC2 mediates podocyte injury in diabetes. RESULTS: High glucose (HG) induces podocyte injury reflected by alteration in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway...
July 8, 2016: Antioxidants & Redox Signaling
Leopoldo Raij, Runxia Tian, Jenny S Wong, John C He, Kirk N Campbell
Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA)...
December 1, 2016: American Journal of Physiology. Renal Physiology
Nadezhda N Zheleznova, Chun Yang, Allen W Cowley
Nox4 and Nox2 are the most abundant NADPH oxidases (Nox) in the kidney and have been shown to contribute to hypertension, renal oxidative stress, and injury in Dahl salt-sensitive (SS) hypertensive rats. The present study focused on the role of Nox4 and p67phox/Nox2 in the generation of H2O2 and O2 (·-) in the renal medullary thick ascending limb of Henle (mTAL) of SS rats in response to increasing luminal flow (from 5 to 20 nl/min). Nox4 and p67phox/Nox2 genes were found to be expressed in the mTAL of SS rats...
August 1, 2016: American Journal of Physiology. Renal Physiology
Samy L Habib, Hanna E Abboud
Reactive oxygen species (ROS) are an important endogenous source of DNA damage and oxidative stress in all cell types. Deficiency in tuberin resulted in increased oxidative DNA damage in renal cells. In this study, the role of tuberin in the regulating of ROS and NADPH oxidases was investigated. Formation of ROS and activity of NADPH oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells...
August 2016: Cancer Science
Xiao-Qiang Li, Wen Tian, Xiao-Xiao Liu, Kai Zhang, Jun-Cheng Huo, Wen-Juan Liu, Ping Li, Xiong Xiao, Ming-Gao Zhao, Wei Cao
Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms...
2016: Scientific Reports
Kyong-Jin Jung, Kyoung-Jin Min, Jeen-Woo Park, Kwon Moo Park, Taeg Kyu Kwon
Fibrosis represents a common pathway to end-stage renal disease. Transforming growth factor-β (TGF-β) plays a critical role in the progression of kidney fibrosis. In the present study, we explored the effect of carnosic acid (CA) against TGF-β-induced fibroblast activation in vitro and unilateral ureteral obstruction (UUO)-induced kidney fibrosis in vivo. CA attenuated TGF-β-induced up-regulation of profibrogenic proteins, α-smooth muscle actin (α-SMA), collagen I (COLI), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1) in kidney fibroblast cells (NRK-49F)...
August 2016: Free Radical Biology & Medicine
Xi Cheng, Xizi Zheng, Yi Song, Lei Qu, Jiawei Tang, Liqiang Meng, Yu Wang
BACKGROUND: Oxidative stress has been identified as an important pathogenesis mechanism in the development of renal interstitial fibrosis in unilateral ureteral obstruction (UUO). Previous studies have demonstrated increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOXs) in response to UUO. We aimed to investigate whether NOXs activation was involved in the development of renal fibrosis in UUO by contribution to oxidative stress and the potential mechanism in the present study...
August 2016: Free Radical Research
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