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https://www.readbyqxmd.com/read/28473473/the-emerging-role-of-nadph-oxidase-nox5%C3%A2-in-vascular-disease
#1
EDITORIAL
Jay C Jha, Anna M D Watson, Geetha Mathew, Lisanne C de Vos, Karin Jandeleit-Dahm
Oxidative stress is a consequence of up-regulation of pro-oxidant enzyme-induced reactive oxygen species (ROS) production and concomitant depletion of antioxidants. Elevated levels of ROS act as an intermediate and are the common denominator for various diseases including diabetes-associated macro-/micro-vascular complications and hypertension. A range of enzymes are capable of generating ROS, but the pro-oxidant enzyme family, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), are the only enzymes known to be solely dedicated to ROS generation in the vascular tissues, kidney, aortas and eyes...
May 1, 2017: Clinical Science (1979-)
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
#2
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 22, 2017: European Journal of Pharmacology
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
#3
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
#4
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/28323024/ppar%C3%AE-activation-by-mhy908-attenuates-age-related-renal-inflammation-through-modulation-of-the-ros-akt-foxo1-pathway
#5
Ye Ra Kim, Eun Kyeong Lee, Dae Hyun Kim, Kyung Mok Kim, Bonggi Lee, Hye Jin An, June Whoun Park, Kyoung Mi Moon, Min Hi Park, Ki Wung Chung, Ji Young Park, Seong Jin Kim, Hwi Young Yun, Sujin Son, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
2-[4-(5-Chlorobenzothiazothiazol-2-yl)phenoxy]-2-methyl-propionic acid (MHY908) has been shown to prevent insulin resistance-induced hyperinsulinemia in aged rats. However, the mechanism underlying MHY908-mediated amelioration of renal inflammation with insulin resistance during aging remains unknown. This study investigated the effects of MHY908 on age-related changes in the IRS/Akt/forkhead box (FoxO) 1 signaling pathway in the kidneys of aged rats and HEK293T cells. Experiments were performed in young, old, and MHY908-fed old rats (1mg or 3mg/kg/day MHY908 for 4 weeks)...
June 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28249219/psoriasis-like-inflammation-leads-to-renal-dysfunction-via-upregulation-of-nadph-oxidases-and-inducible-nitric-oxide-synthase
#6
Naif O Al-Harbi, Ahmed Nadeem, Mushtaq A Ansari, Mohammed M Al-Harbi, Moureq R Alotaibi, Abdulaziz M S AlSaad, Sheikh F Ahmad
Psoriatic patients have systemic inflammation as well as oxidative stress, which are associated with cardiovascular disorders such as atherosclerosis, hypertension myocardial infarction, and stroke. Psoriasis has also been shown to be associated with kidney disease in several studies. Both disorders also have strong component of oxidative stress which usually emanates from NADPH oxidases (NOXs) and inducible nitric oxide synthase (iNOS). However, whether psoriatic inflammation leads to renal oxidative stress and dysfunction remains unexplored...
February 26, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28211114/magnesium-lithospermate-b-from-salvia-miltiorrhiza-bunge-ameliorates-aging-induced-renal-inflammation-and-senescence-via-nadph-oxidase-mediated-reactive-oxygen-generation
#7
Chan Hum Park, Sung Ho Shin, Eun Kyeong Lee, Dae Hyun Kim, Min-Jo Kim, Seong-Soo Roh, Takako Yokozawa, Hae Young Chung
The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species...
February 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28188286/hydrogen-sulfide-inhibits-high-glucose-induced-nadph-oxidase-4-expression-and-matrix-increase-by-recruiting-inducible-nitric-oxide-synthase-in-kidney-proximal-tubular-epithelial-cells
#8
Hak Joo Lee, Doug Yoon Lee, Meenalakshmi M Mariappan, Denis Feliers, Goutam Ghosh-Choudhury, Hanna E Abboud, Yves Gorin, Balakuntalam S Kasinath
High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H2S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H2S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H2S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H2S...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28165467/apx-115-a-first-in-class-pan-nadph-oxidase-nox-inhibitor-protects-db-db-mice-from-renal-injury
#9
Jin Joo Cha, Hye Sook Min, Ki Tae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyun Wook Kim, Ji Eun Lee, Jee Young Han, Gayoung Lee, Hun Joo Ha, Yun Soo Bae, Sae Rom Lee, Sung Hwan Moon, Sung Chan Lee, Ganghyun Kim, Young Sun Kang, Dae Ryong Cha
Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol...
April 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28138709/trpm8-downregulation-by-angiotensin-ii-in-vascular-smooth-muscle-cells-is-involved-in-hypertension
#10
Fang Huang, Min Ni, Jing-Ming Zhang, Dong-Jie Li, Fu-Ming Shen
Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28132913/nebivolol-prevents-ethanol-induced-reactive-oxygen-species-generation-and-lipoperoxidation-in-the-rat-kidney-by-regulating-nadph-oxidase-activation-and-expression
#11
Gabriel T do Vale, Natália A Gonzaga, Janaina A Simplicio, Carlos R Tirapelli
We studied whether the β1-adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O2(-)) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28116040/mitotempo-prevents-oxalate-induced-injury-in-nrk-52e-cells-via-inhibiting-mitochondrial-dysfunction-and-modulating-oxidative-stress
#12
Jiaqiao Zhang, Qing Wang, Chuou Xu, Yuchao Lu, Henglong Hu, Baolong Qin, Yufeng Wang, Deng He, Cong Li, Xiao Yu, Shaogang Wang, Jihong Liu
As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28063381/brd4-inhibition-attenuates-unilateral-ureteral-obstruction-induced-fibrosis-by-blocking-tgf-%C3%AE-mediated-nox4-expression
#13
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)...
April 2017: Redox Biology
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/27999546/protocatechuic-aldehyde-attenuates-cisplatin-induced-acute-kidney-injury-by-suppressing-nox-mediated-oxidative-stress-and-renal-inflammation
#15
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
https://www.readbyqxmd.com/read/27960539/c-x-c-chemokine-receptor-type-4-plays-a-crucial-role-in-mediating-oxidative-stress-induced-podocyte-injury
#16
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 C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (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...
March 28, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27924932/nadph-oxidase-4-deficiency-increases-tubular-cell-death-during-acute-ischemic-reperfusion-injury
#17
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
https://www.readbyqxmd.com/read/27898405/n-acetyl-cysteine-attenuated-the-deleterious-effects-of-advanced-glycation-end-products-on-the-kidney-of-non-diabetic-rats
#18
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
https://www.readbyqxmd.com/read/27763643/mitochondrial-angiotensin-receptors-in-dopaminergic-neurons-role-in-cell-protection-and-aging-related-vulnerability-to-neurodegeneration
#19
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
https://www.readbyqxmd.com/read/27649495/renoprotective-effects-of-atorvastatin-in-diabetic-mice-downregulation-of-rhoa-and-upregulation-of-akt-gsk3
#20
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
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