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NADPH oxidase and renal

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https://www.readbyqxmd.com/read/29051480/nox4-functions-as-a-mitochondrial-energetic-sensor-coupling-cancer-metabolic-reprogramming-to-drug-resistance
#1
Karthigayan Shanmugasundaram, Bijaya K Nayak, William E Friedrichs, Dharam Kaushik, Ronald Rodriguez, Karen Block
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2)...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29032812/matrix-vesicles-induce-calcification-of-recipient-vascular-smooth-muscle-cells-through-multiple-signaling-pathways
#2
Neal X Chen, Kalisha D O'Neill, Sharon M Moe
In patients with chronic kidney and end-stage renal diseases, the major risk factor for progression of arterial calcification is the presence of existing (baseline) calcification. Here, we tested whether calcification of arteries is extended from calcified vascular smooth muscle cells (VSMCs) to adjacent normal cells by matrix vesicle-induced alteration of cell signaling. Matrix vesicles isolated from VSMC of rats with chronic kidney disease were co-cultured with VSMCs from normal littermates. Endocytosis of vesicles by recipient cells was confirmed by confocal microscopy...
October 9, 2017: Kidney International
https://www.readbyqxmd.com/read/29032117/salvia-miltiorrhiza-protects-adenine-induced-chronic-renal-failure-by-regulating-the-metabolic-profiling-and-modulating-the-nadph-oxidase-ros-erk-and-tgf-%C3%AE-smad-signaling-pathways
#3
Hongdie Cai, Shulan Su, Yonghui Li, Huiting Zeng, Zhenhua Zhu, Jianming Guo, Yue Zhu, Sheng Guo, Li Yu, Dawei Qian, Yuping Tang, Jinao Duan
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic renal failure (CRF) is defined as a progressive and irreversible loss of renal function and associated with inflammation and oxidative stress. Salvia miltiorrhiza (SM) is an important Chinese herb used in traditional Chinese medicine with notable effects on CRF. It significantly inhibited the elevation of serum creatinine (Scr), blood urea nitrogen (BUN) and urine protein (UP) in adenine-induced CRF rats, while the action mechanism need to be illuminated deeply...
October 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28942145/gut-microbial-metabolite-tmao-contributes-to-renal-dysfunction-in-a-mouse-model-of-diet-induced-obesity
#4
Guangping Sun, Zhongmin Yin, Naiquan Liu, Xiaohui Bian, Rui Yu, Xiaoxiao Su, Beiru Zhang, Yanqiu Wang
Emerging evidence shows that obesity induces renal injury and is an independent risk factor for the development of chronic kidney disease (CKD), even without diabetes or hyperglycemia. Although multiple metabolic factors have been suggested to account for obesity-associated renal injury, the precious underlying mechanisms are not completely understood. Recent study shows that increased trimethylamine N-Oxide (TMAO), a gut microbiota-generated metabolite, directly contributes to renal interstitial fibrosis and dysfunction...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28894570/nadph-oxidase-inhibitor-diphenyleneiodonium-prevents-necroptosis-in-hk-2-cells
#5
Wei Dong, Zhilian Li, Yuanhan Chen, Li Zhang, Zhiming Ye, Huaban Liang, Ruizhao Li, Lixia Xu, Bin Zhang, Shuangxin Liu, Weidong Wang, Chunling Li, Jialun Luo, Wei Shi, Xinling Liang
The aim of the present study was to investigate the protective effect of the NADPH oxidase inhibitor, diphenyleneiodonium (DPI) against necroptosis in renal tubular epithelial cells. A necroptosis model of HK-2 cells was established using tumor necrosis factor-α, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone and antimycin A (collectively termed TZA), as in our previous research. The necroptosis inhibitor, necrostatin-1 (Nec-1) or the NADPH oxidase inhibitor, DPI were administered to the necroptosis model...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28878231/dietary-iron-restriction-alleviates-renal-tubulointerstitial-injury-induced-by-protein-overload-in-mice
#6
Yasumasa Ikeda, Yuya Horinouchi, Hirofumi Hamano, Tasuku Hirayama, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-Ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya, Toshiaki Tamaki
Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855243/update-on-angiotensin-ii-new-endocrine-connections-between-the-brain-adrenal-glands-and-the-cardiovascular-system
#7
REVIEW
Frans H H Leenen, Mordecai P Blaustein, John M Hamlyn
In the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na(+)] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits and maintains/further increases the activity of angiotensinergic pathways...
October 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28840362/effect-of-endoplasmic-reticulum-stress-inhibition-on-hyperoxaluria-induced-oxidative-stress-influence-on-cellular-ros-sources
#8
Rishi Bhardwaj, Chanderdeep Tandon, Devinder K Dhawan, Tanzeer Kaur
PURPOSE: Hyperoxaluria-induced calcium oxalate crystallisation is associated with the generation of reactive oxygen species (ROS) via mitochondria and NADPH oxidase. Endoplasmic reticulum (ER) has emerged as an organelle which could influence mitochondrial functioning and ROS generation. Plugging an upstream pathway of mitochondrial and NADPH oxidase-induced ROS generation may have better prophylaxis. Therefore, we propose to investigate the linkage of hyperoxaluria-induced ROS generation with ER stress by inhibiting the later with 4-Phenylbutyric acid (4-PBA)...
August 24, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28822538/smooth-muscle-nitric-oxide-responsiveness-and-clinical-maturation-of-hemodialysis-arteriovenous-fistulae
#9
Xiaoyong Tong, Xiuyun Hou, Christopher Wason, Tal Kopel, Richard A Cohen, Laura M Dember
The arteriovenous fistula is the preferred type of hemodialysis vascular access for patients with end-stage renal disease, but a high proportion of newly created fistulas fail to mature for use. Stenosis caused by neointimal hyperplasia often is present in fistulas with maturation failure, suggesting that local mechanisms controlling vascular smooth muscle cell (SMC) migration and proliferation are important contributors to maturation failure. SMCs cultured from explants of vein tissue obtained at the time of fistula creation from 19 patients with end-stage renal disease were studied to determine whether smooth muscle responsiveness to nitric oxide is associated with fistula maturation outcomes...
September 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28820443/omega-3-polyunsaturated-fatty-acids-improve-endothelial-dysfunction-in-chronic-renal-failure-role-of-enos-activation-and-of-oxidative-stress
#10
Michela Zanetti, Gianluca Gortan Cappellari, Davide Barbetta, Annamaria Semolic, Rocco Barazzoni
BACKGROUND: Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (n-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether n-3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial nitric oxide synthase (eNOS) function and oxidative stress. METHODS: 5/6 nephrectomized male Wistar rats (CKD; n = 10) and sham operated animals (SHAM; n = 10) were treated for 6 weeks with standard diet...
August 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28805491/intermedin-inhibits-unilateral-ureteral-obstruction-induced-oxidative-stress-via-nadph-oxidase-nox4-and-camp-dependent-mechanisms
#11
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yue Qi, Yun Fan, Zhiqiang Peng
NADPH oxidase Nox4-derived reactive oxygen species (ROS) play important roles in renal fibrosis. Our previous study demonstrated that intermedin (IMD) alleviated unilateral ureteral obstruction (UUO)-induced renal fibrosis by inhibition of ROS. However, the precise mechanisms remain unclear. Herein, we investigated the effect of IMD on Nox4 expression and NADPH oxidase activity in rat UUO model, and explored if these effect were achieved through cAMP-PKA pathway, the important post-receptor signal transduction pathway of IMD, in TGF-β1-stimulated rat proximal tubular cell (NRK-52E)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28782595/dhea-supplementation-to-dexamethasone-treated-rabbits-alleviates-oxidative-stress-in-kidney-cortex-and-attenuates-albuminuria
#12
Anna Kiersztan, Nina Trojan, Aleksandra Tempes, Paweł Nalepa, Joanna Sitek, Katarzyna Winiarska, Michał Usarek
Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated...
August 4, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28761330/epigenetic-memory-of-oxidative-stress-does-nephrilin-exert-its-protective-effects-via-rac1
#13
Desmond D Mascarenhas, David N Herndon, Istvan Arany
AIM: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2), exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox) via PKCs, Prex1 and p66shc...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28754616/role-of-uremic-toxin-indoxyl-sulfate-in-the-progression-of-cardiovascular-disease
#14
REVIEW
Huichang Gao, Shan Liu
The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate oxidative stress, which in turn contributes to the progression of vascular disorders and its resultant coronary artery disease. Recent research have demonstrated the adverse effects of indoxyl sulfate on the heart, together with the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might contribute to high prevalence of CVD in CKD...
July 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28753620/treatment-combining-aliskiren-with-paricalcitol-is-effective-against-progressive-renal-tubulointerstitial-fibrosis-via-dual-blockade-of-intrarenal-renin
#15
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Ho-Shik Kim
The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells...
2017: PloS One
https://www.readbyqxmd.com/read/28748119/uric-acid-in-the-pathogenesis-of-metabolic-renal-and-cardiovascular-diseases-a-review
#16
REVIEW
Usama A A Sharaf El Din, Mona M Salem, Dina O Abdulazim
The association between uric acid (UA) on one side and systemic hypertension (Htn), dyslipidemia, glucose intolerance, overweight, fatty liver, renal disease and cardiovascular disease (CVD) on the other side is well recognized. However, the causal relationship between UA and these different clinical problems is still debatable. The recent years have witnessed hundreds of experimental and clinical trials that favored the opinion that UA is a probable player in the pathogenesis of these disease entities. These studies disclosed the strong association between hyperuricemia and metabolic syndrome (MS), obesity, Htn, type 2 diabetes mellitus (DM), non-alcoholic fatty liver disease, hypertriglyceridemia, acute kidney injury, chronic kidney disease (CKD), coronary heart disease (CHD), heart failure and increased mortality among cardiac and CKD patients...
September 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28747378/nadph-oxidase-nox5-accelerates-renal-injury-in-diabetic-nephropathy
#17
Jay C Jha, Claudine Banal, Jun Okabe, Stephen P Gray, Thushan Hettige, Bryna S M Chow, Vicki Thallas-Bonke, Lisanne De Vos, Chet E Holterman, Melinda T Coughlan, David A Power, Alison Skene, Elif I Ekinci, Mark E Cooper, Rhian M Touyz, Chris R Kennedy, Karin Jandeleit-Dahm
NADPH oxidase-derived excessive production of reactive oxygen species (ROS) in the kidney plays a key role in mediating renal injury in diabetes. Pathological changes in diabetes include mesangial expansion and accumulation of extracellular matrix (ECM) leading to glomerulosclerosis. There is a paucity of data about the role of the Nox5 isoform of NADPH oxidase in animal models of diabetic nephropathy since Nox5 is absent in the mouse genome. Thus, we examined the role of Nox5 in human diabetic nephropathy in human mesangial cells and in an inducible human Nox5 transgenic mouse exposed to streptozotocin-induced diabetes...
October 2017: Diabetes
https://www.readbyqxmd.com/read/28738532/genipin-attenuates-cisplatin-induced-nephrotoxicity-by-counteracting-oxidative-stress-inflammation-and-apoptosis
#18
Eglal Mahgoub, Shanmugam Muthu Kumaraswamy, Kamal Hassan Kader, Balaji Venkataraman, Shreesh Ojha, Ernest Adeghate, Mohanraj Rajesh
Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28734244/renal-denervation-attenuates-hypertension-and-renal-dysfunction-in-a-model-of-cardiovascular-and-renal-disease-which-is-associated-with-reduced-nadph-and-xanthine-oxidase-activity
#19
Maria Peleli, Peter Flacker, Zhengbing Zhuge, Cristina Gomez, Craig E Wheelock, A Erik G Persson, Mattias Carlstrom
Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species...
July 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28722118/at2-r-deficiency-mediated-podocyte-loss-via-activation-of-ectopic-hedgehog-interacting-protein-hhip-gene-expression
#20
Min-Chun Liao, Xin-Ping Zhao, Shiao-Ying Chang, Chao-Sheng Lo, Isabelle Chenier, Tomoko Takano, Julie R Ingelfinger, Shao-Ling Zhang
Angiotensin II type 2 receptor (AT2 R) deficiency in AT2 R knockout (KO) mice has been linked to congenital abnormalities of the kidney and urinary tract; however, the mechanisms by which this occurs are poorly understood. In this study, we examined whether AT2 R deficiency impaired glomerulogenesis and mediated podocyte loss/dysfunction in vivo and in vitro. Nephrin-cyan fluorescent protein (CFP)-transgenic (Tg) and Nephrin/AT2 RKO mice were used to assess glomerulogenesis, while wild-type and AT2 RKO mice were used to evaluate maturation of podocyte morphology/function...
July 19, 2017: Journal of Pathology
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