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https://www.readbyqxmd.com/read/28811547/up-regulation-of-nadph-oxidase-mediated-redox-signaling-contributes-to-the-loss-of-barrier-function-in-krit1-deficient-endothelium
#1
Luca Goitre, Peter V DiStefano, Andrea Moglia, Nicholas Nobiletti, Eva Baldini, Lorenza Trabalzini, Julie Keubel, Eliana Trapani, Vladimir V Shuvaev, Vladimir R Muzykantov, Ingrid H Sarelius, Saverio Francesco Retta, Angela J Glading
The intracellular scaffold KRIT1/CCM1 is an established regulator of vascular barrier function. Loss of KRIT1 leads to decreased microvessel barrier function and to the development of the vascular disorder Cerebral Cavernous Malformation (CCM). However, how loss of KRIT1 causes the subsequent deficit in barrier function remains undefined. Previous studies have shown that loss of KRIT1 increases the production of reactive oxygen species (ROS) and exacerbates vascular permeability triggered by several inflammatory stimuli, but not TNF-α...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811292/dapagliflozin-slows-the-progression-of-the-renal-and-liver-fibrosis-associated-with-type-2-diabetes
#2
Li Tang, Yuanyuan Wu, Mi Tian, C David Sjostrom, Ulrika Johansson, Xiao-Rong Peng, David M Smith, Yufeng Huang
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic oral agents indicating promising effects on cardiovascular and renal end points. However, the renoprotective effects of SGLT2 inhibitors are not fully understood. Also, metabolic effects of SGLT2 inhibition on other organ systems such as effects on hepatic steatosis are not fully understood. This study sought to address these questions by treating 18week-old uninephrectomized db/db mice with a selective SGLT2 inhibitor dapagliflozin...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28809856/decreased-nox2-expression-in-the-brain-of-patients-with-bipolar-disorder-association-with-valproic-acid-prescription-and-substance-abuse
#3
T Seredenina, S Sorce, F R Herrmann, X-J Ma Mulone, O Plastre, A Aguzzi, V Jaquet, K-H Krause
Neuroinflammation and increased oxidative stress are believed to contribute to the development of psychiatric diseases. Animal studies have implicated NADPH oxidases (NOX) as relevant sources of reactive oxygen species in the brain. We have analyzed the expression of NOX isoforms in post-mortem brain samples from patients with psychiatric disorders (schizophrenia, bipolar disorder) and non-psychiatric subjects. Two collections from the Stanley Medical Research Institute were studied: the Array Collection (RNA, 35 individuals per group), and a neuropathology consortium collection (paraffin-embedded sections, 15 individuals per group)...
August 15, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28808291/glp-1-inhibits-high-glucose-induced-oxidative-injury-of-vascular-endothelial-cells
#4
Quan Li, Yajun Lin, Shu Wang, Lina Zhang, Lixin Guo
The aim of this work was to evaluate the effects of glucagon-like peptide-1 (GLP-1) on high-glucose-induced oxidative stress and investigate the possible mechanisms underlying this process. We measured reactive oxygen species (ROS) production, cell apoptosis, the expression of NOX4 and its subunits, and p47phox translocation in human umbilical vein endothelial cells (HUVECs). An experimental type 2 diabetes model was induced using streptozotocin in male Sprague-Dawley rats. Fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and free fatty acid (FFA) were measured...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806703/nox4-mediated-ros-production-induces-apoptotic-cell-death-via-down-regulation-of-c-flip-and-mcl-1-expression-in-combined-treatment-with-thioridazine-and-curcumin
#5
Seung Un Seo, Tae Hwan Kim, Dong Eun Kim, Kyoung-Jin Min, Taeg Kyu Kwon
Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA...
August 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28805491/intermedin-inhibits-unilateral-ureteral-obstruction-induced-oxidative-stress-via-nadph-oxidase-nox4-and-camp-dependent-mechanisms
#6
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/28793782/direct-activation-of-nadph-oxidase-2-by-2-deoxyribose-1-phosphate-triggers-nuclear-factor-kappa-b-dependent-angiogenesis
#7
Dina Vara, Joanna M Watt, Tiago M Fortunato, Harry Mellor, Matthew Burgess, Kate Wicks, Kimberly Mace, Shaun Reeksting, Anneke T Lubben, Caroline Pd Wheeler-Jones, Giordano Pula
AIMS: Deoxyribose-1-phosphate (dRP) is a pro-angiogenic paracrine stimulus released by cancer cells, platelets and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells. RESULTS: Live cell imaging, electron paramagnetic resonance (EPR), pull-down of dRP-interacting proteins followed by immunoblotting, gene silencing of different NOXs and their regulatory co-subunits by siRNA transfection, and experiments with inhibitors of the sugar transporter GLUT1 were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NADPH oxidase 2 (NOX2) complex, but not NOX4...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28793197/glycosylation-with-o-linked-%C3%AE-n-acetylglucosamine-o-glcnac-induces-vascular-dysfunction-via-production-of-superoxide-anion-reactive-oxygen-species
#8
Leonardo Souza-Silva, Rhéure Alves-Lopes, Jéssica Silva Miguez, Vanessa Dela Justina, Karla Bianca Neves, Fabíola Leslie Mestriner, Rita C Tostes, Fernanda Regina Giachini, Victor V Lima
Overproduction of superoxide anion (•O2-) and O-linked β-N-acetylglucosamine (O-GlcNAc)-modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2- production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cell (VSMCs) were incubated with vehicle (methanol) or PUGNAc (100 µM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and Tiron, suggesting that •O2- contributes to endothelial dysfunction under augmented O-GlcNAc levels...
August 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28774949/renoprotective-effect-of-topiroxostat-via-antioxidant-activity-in-puromycin-aminonucleoside-nephrosis-rats
#9
Yosuke Kawamorita, Takeshi Shiraishi, Yoshifuru Tamura, Takanori Kumagai, Shigeru Shibata, Yoshihide Fujigaki, Makoto Hosoyamada, Takahiko Nakagawa, Shunya Uchida
Topiroxostat is a novel inhibitor of xanthine oxidase, and is postulated to exert a renoprotective effect. Puromycin aminonucleoside nephrosis (PAN) is a rat model of minimal change nephrotic syndrome. In this study, we examined whether topiroxostat ameliorates the kidney injury in PAN rats that was induced by a single intraperitoneal injection of PA (100 mg/kg body weight). Rats were divided into four groups: control rats, PAN rats, control rats treated with topiroxostat (1.0 mg/kg/day), and PAN rats treated with topiroxostat...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28772089/fructose-rich-diet-differently-affects-angiotensin-ii-receptors-content-in-the-nucleus-and-a-plasma-membrane-fraction-of-visceral-adipose-tissue
#10
Maja Bundalo, Ana Djordjevic, Biljana Bursac, Maja Zivkovic, Goran Koricanac, Aleksandra Stankovic
The adipose tissue renin-angiotensin system (RAS) is proposed to be a pathophysiological link between adipose tissue dysregulation and metabolic disorders induced by fructose rich diet (FRD). RAS can act intracellularly. We hypothesized that adipocytes nuclear membranes possess angiotensin receptors type 1 and type 2 (AT1R and AT2R) that couple to nuclear signaling pathways and regulate oxidative gene expression under the FRD. We analyzed the effect of nine-week consumption of 10% fructose solution on biochemical parameters, adipocyte morphology and expression of AT1R, AT2R, AT1R-associated protein (ATRAP), NOX4, MMP-9, and MnSOD in adipose tissue of Wistar rats...
August 3, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28771600/eicosapentaenoic-acid-prevents-arterial-calcification-in-klotho-mutant-mice
#11
Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Kei Yunoki, Yasushi Koyama, Minoru Satoh, Megumi Kondo, Kazuhiro Osawa, Omer F Hatipoglu, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito
BACKGROUND: The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/28753620/treatment-combining-aliskiren-with-paricalcitol-is-effective-against-progressive-renal-tubulointerstitial-fibrosis-via-dual-blockade-of-intrarenal-renin
#12
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/28751569/cyld-deubiquitinates-nicotinamide-adenine-dinucleotide-phosphate-oxidase-4-contributing-to-adventitial-remodeling
#13
Bing Yu, Ziyi Liu, Yi Fu, Yingbao Wang, Lu Zhang, Zeyu Cai, Fang Yu, Xian Wang, Jun Zhou, Wei Kong
OBJECTIVE: Transdifferentiation of adventitial fibroblasts (AFs) into myofibroblasts plays a critical role during the vascular remodeling that occurs during atherosclerosis, restenosis, and aortic aneurysm. The ubiquitination/deubiquitination regulatory system is essential for the quality control of proteins. The involvement of ubiquitination/deubiquitination during AF transdifferentiation remains largely unknown. In this study, we determined the role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF differentiation and activation in vitro and in vivo...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751023/lysocardiolipin-acyltransferase-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation
#14
Long Shuang Huang, Peiyue Jiang, Carol Feghali-Bostwick, Sekhar P Reddy, Joe G N Garcia, Viswanathan Natarajan
Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a key role in mitochondrial function and vascular development. We previously reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells correlated with poor pulmonary function outcomes and decreased survival in IPF patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression and oxidative stress are known to contribute to lung fibroblast differentiation and progression of fibrosis...
July 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28748915/the-endoplasmic-reticulum-stress-autophagy-pathway-is-involved-in-apelin-13-induced-cardiomyocyte-hypertrophy-in-vitro
#15
Feng Xie, Di Wu, Shi-Fang Huang, Jian-Gang Cao, He-Ning Li, Lu He, Mei-Qing Liu, Lan-Fang Li, Lin-Xi Chen
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28743960/nadph-oxidase-4-is-required-for-the-generation-of-macrophage-migration-inhibitory-factor-and-host-defense-against-toxoplasma-gondii-infection
#16
Ji Hye Kim, Jina Lee, Su-Jin Bae, Yeeun Kim, Byung-Joon Park, Jae-Won Choi, Jaeyul Kwon, Guang-Ho Cha, Heon Jong Yoo, Eun-Kyeong Jo, Yun Soo Bae, Young-Ha Lee, Jae-Min Yuk
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated. Here, we found that T. gondii-mediated ROS production was required for the upregulation of macrophage migration inhibitory factor (MIF) mRNA and protein levels via activation of mitogen-activated protein kinase and nuclear factor-κB signaling in macrophages...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28740353/anti-apoptotic-effect-of-banhasasim-tang-on-chronic-acid-reflux-esophagitis
#17
Mi-Rae Shin, Hyo-Jin An, Bu-Il Seo, Seong-Soo Roh
AIM: To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. METHODS: A surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting...
July 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28739802/tgf-%C3%AE-1-regulates-the-expression-and-transcriptional-activity-of-taz-via-a-smad3-independent-myocardin-related-transcription-factor-mediated-mechanism
#18
Maria Zena Miranda, Janne Folke Bialik, Pam Speight, Qinghong Dan, Tony Yeung, Katalin Szászi, Stine F Pedersen, András Kapus
Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-β1 (TGFβ) effector Smad3 regulate a common set of genes, can physically interact and exhibit multilevel crosstalk regulating cell fate-determining and fibrogenic pathways. However, a key aspect of this crosstalk, TGFβ-mediated regulation of TAZ or YAP expression remains uncharacterized. Here, we show that TGFβ induces robust TAZ but not YAP protein expression in both mesenchymal and epithelial cells. TAZ levels, and to a lesser extent YAP levels, also increased during experimental kidney fibrosis...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28737709/regulation-and-modulation-of-human-dna-polymerase-%C3%AE-activity-and-function
#19
REVIEW
Marietta Y W T Lee, Xiaoxiao Wang, Sufang Zhang, Zhongtao Zhang, Ernest Y C Lee
This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on the mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair...
July 24, 2017: Genes
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#20
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
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