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https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#1
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28630313/targeting-reactive-nitrogen-species-suppresses-hereditary-pancreatic-cancer
#2
Mo Li, Qian Chen, Teng Ma, Xiaochun Yu
Germline mutation of BRCA2 induces hereditary pancreatic cancer. However, how BRCA2 mutation specifically induces pancreatic tumorigenesis remains elusive. Here, we have examined a mouse model of Brca2-deficiency-induced pancreatic tumors and found that excessive reactive nitrogen species (RNS), such as nitrite, are generated in precancerous pancreases, which induce massive DNA damage, including DNA double-strand breaks. RNS-induced DNA lesions cause genomic instability in the absence of Brca2. Moreover, with the treatment of antioxidant tempol to suppress RNS, not only are DNA lesions significantly reduced, but also the onset of pancreatic cancer is delayed...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#3
Soledad Pitra, Javier E Stern
Recent studies support an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic sympathetic and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We recently showed that PRR is expressed in VP neurons, and that their activation increases neuronal activity...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28603016/rapid-repeatable-in%C3%A2-vivo-detection-of-retinal-reactive-oxygen-species
#4
Ning Fan, Sean M Silverman, Yang Liu, Xizhen Wang, Byung-Jin Kim, Liping Tang, Abbot F Clark, Xuyang Liu, Iok-Hou Pang
Oxidative injuries, such as those related to reactive oxygen species (ROS), have been implicated in various retinal and optic nerve disorders. Many ROS detection methods have been developed. Although widely utilized, many of these methods are useful only in post mortem tissues, or require relatively expensive equipment, or involve intraocular injection. In the present study, we demonstrated and characterized a chemiluminescent probe L-012 as a noninvasive, in vivo ROS detection agent in the mouse retina. Using optic nerve crush (ONC) and retinal ischemia/reperfusion (I/R) as injury models, we show that L-012 produced intensive luminescent signals specifically in the injured eyes...
June 8, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28600985/nox2-contributes-to-hyperinsulinemia-induced-redox-imbalance-and-impaired-vascular-function
#5
Abeer M Mahmoud, Mohamed M Ali, Edwin R Miranda, Jacob T Mey, Brian K Blackburn, Jacob M Haus, Shane A Phillips
Insulin resistance promotes vascular endothelial dysfunction and subsequent development of cardiovascular disease. Previously we found that skeletal muscle arteriolar flow-induced dilation (FID) was reduced following a hyperinsulinemic clamp in healthy adults. Therefore, we hypothesized that hyperinsulinemia, a hallmark of insulin resistance, contributes to microvascular endothelial cell dysfunction via inducing oxidative stress that is mediated by NADPH oxidase (Nox) system. We examined the effect of insulin, at levels that are comparable with human hyperinsulinemia on 1) FID of isolated arterioles from human skeletal muscle tissue in the presence and absence of Nox inhibitors and 2) human adipose microvascular endothelial cell (HAMECs) expression of nitric oxide (NO), endothelial NO synthase (eNOS), and Nox-mediated oxidative stress...
June 3, 2017: Redox Biology
https://www.readbyqxmd.com/read/28598474/anisotropic-longitudinal-electronic-relaxation-affects-dnp-at-cryogenic-temperatures
#6
E M M Weber, H Vezin, J G Kempf, G Bodenhausen, D Abergél, D Kurzbach
We report the observation of anisotropic longitudinal electronic relaxation in nitroxide radicals under typical dynamic nuclear polarization conditions. This anisotropy affects the efficiency of dynamic nuclear polarization at cryogenic temperatures of 4 K and high magnetic fields of 6.7 T. Under our experimental conditions, the electron paramagnetic resonance spectrum of nitroxides such as TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) is only partly averaged by electronic spectral diffusion, so that the relaxation times T1e(ω) vary across the spectrum...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28589150/tempol-a-superoxide-dismutase-mimetic-agent-inhibits-superoxide-anion-induced-inflammatory-pain-in-mice
#7
Catia C F Bernardy, Ana C Zarpelon, Felipe A Pinho-Ribeiro, Cássia Calixto-Campos, Thacyana T Carvalho, Victor Fattori, Sergio M Borghi, Rubia Casagrande, Waldiceu A Verri
The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91(phox), Nrf2, GFAP, and Iba-1, were evaluated...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28584168/palmitate-and-oleate-exert-differential-effects-on-insulin-signalling-and-glucose-uptake-in-human-skeletal-muscle-cells
#8
Selina Mäkinen, Hoang Yen Nguyen, Paulina Skrobuk, Heikki A Koistinen
Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pre-treated with palmitate, oleate, or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [3H]-2-Deoxy-D-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX™...
June 5, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28575410/enhanced-endothelin-1-rho-kinase-signaling-and-coronary-microvascular-dysfunction-in-hypertensive-myocardial-hypertrophy
#9
Shu-Huai Tsai, Guangrong Lu, Xin Xu, Yi Ren, Travis W Hein, Lih Kuo
Aims: Hypertensive cardiac hypertrophy is associated with reduced coronary flow reserve, but its impact on coronary flow regulation and vasomotor function remains incompletely understood and requires further investigation. Methods and results: Left ventricular hypertrophy was induced in mice by transverse aortic coarctation (TAC) for 4 weeks. The left coronary artery blood velocity (LCABV) and myocardium lactate level were measured following the metabolic activation by isoproterenol...
May 29, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28574428/reduced-dietary-selenium-impairs-vascular-function-by-increasing-oxidative-stress-in-sprague-dawley-rat-aortas
#10
Ana Stupin, Anita Cosic, Sanja Novak, Monika Vesel, Ivana Jukic, Brigita Popovic, Krunoslav Karalic, Zdenko Loncaric, Ines Drenjancevic
This study aimed to determine whether low dietary Se content affects the function and mechanisms mediating the vascular relaxation of rat aortas, and to test the role of oxidative stress in observed differences. Male Sprague Dawley (SD) rats were maintained for 10 weeks on low Se (low-Se group; N = 20) or normal Se content (norm-Se group; N = 20) rat chow. Dose responses to acetylcholine (ACh; 10(-9)-10(-5)M) and the response to reduced pO₂ were tested in noradrenaline-precontracted aortic rings in the absence/presence of the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME), the cyclooxygenase 1 and 2 (COX-1, 2) inhibitor Indomethacin, and the antioxidative agent Tempol in tissue bath...
June 2, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28562691/chronic-treatment-with-paeonol-improves-endothelial-function-in-mice-through-inhibition-of-endoplasmic-reticulum-stress-mediated-oxidative-stress
#11
Ker Woon Choy, Yeh Siang Lau, Dharmani Murugan, Mohd Rais Mustafa
Endoplasmic reticulum (ER) stress leads to endothelial dysfunction which is commonly associated in the pathogenesis of several cardiovascular diseases. We explored the vascular protective effects of chronic treatment with paeonol (2'-hydroxy-4'-methoxyacetophenone), the major compound from the root bark of Paeonia suffruticosa on ER stress-induced endothelial dysfunction in mice. Male C57BL/6J mice were injected intraperitoneally with ER stress inducer, tunicamycin (1 mg/kg/week) for 2 weeks to induce ER stress...
2017: PloS One
https://www.readbyqxmd.com/read/28556994/hyperglycemia-in-pregnant-rats-causes-gender-related-vascular-dysfunction-in-adult-offspring-role-of-cyclooxygenase-2
#12
Francine Gomes de Sá, Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Odair Alves da Silva, Hicla Steffany Moreira, Geórgia Andrade Leal, Marcelo Aurélio da Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
Exposure to maternal hyperglycemia induces hypertension and vascular dysfunction in adult male offspring. Because female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analyzed possible differences relative to gender in blood pressure and vascular function in hyperglycemia-programmed offspring. Hyperglycemia was induced on gestation day 7 (streptozotocin, 50 mg.kg(-1) ). Blood pressure, acetylcholine and phenylephrine/noradrenaline responses were analyzed in aorta and mesenteric resistance arteries (MRA) of 3-, 6- and 12-month-old male and female offspring...
May 30, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#13
Justin P Van Beusecum, Shali Zhang, Anthony K Cook, Edward W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to step-wise changes in renal perfusion pressure...
May 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28533261/the-superoxide-dismutase-mimetic-tempol-does-not-alleviate-glucocorticoid-mediated-rarefaction-of-rat-skeletal-muscle-capillaries
#14
Erin R Mandel, Emily C Dunford, Ghoncheh Abdifarkosh, Patrick C Turnbull, Christopher G R Perry, Michael C Riddell, Tara L Haas
Sustained elevations in circulating glucocorticoids elicit reductions in skeletal muscle microvascular content, but little is known of the underlying mechanisms. We hypothesized that glucocorticoid-induced oxidative stress contributes to this phenomenon. In rats that were implanted with corticosterone (CORT) or control pellets, CORT caused a significant decrease in muscle glutathione levels and a corresponding increase in protein carbonylation, an irreversible oxidative modification of proteins. Decreased endothelial nitric oxide synthase and increased endothelin-1 mRNA levels were detected after 9 days of CORT, and blood flow to glycolytic muscles was diminished...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28532685/nitroxide-4-hydroxy-2-2-6-6-tetramethylpiperidine-1-oxyl-tempol-inhibits-the-reductase-activity-of-protein-disulfide-isomerase-via-covalent-binding-to-the-cys400-residue-on-cxxc-redox-motif-at-the-a-active-site
#15
Gérsika Bitencourt Santos, Lucia Gonzalez-Perilli, Mauricio Mastrogiovanni, Adrián Aicardo, Cláudio Daniel Cerdeira, Andrés Trostchansky, Maísa Ribeiro Pereira Lima Brigagão
BACKGROUND AND AIM: Oxidative stress arising from inflammatory processes is a serious cause of cell and tissue damage. Tempol is an efficient antioxidant with superoxide dismutase-like activity. The purpose of this paper is to address the inhibition of protein disulfide isomerase (PDI), an essential redox chaperone whose active sites contain the Cys-Gly-His-Cys (CXXC) motif, by the nitroxide Tempol. RESULTS: In the presence of Tempol (5-120 μM), the reductase activity of PDI was reversibly affected both in vitro and in activated mice neutrophils, with an IC50 of 22...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28521553/glutaraldehyde-polymerized-hemoglobin-and-tempol-polyhb-tempol-has-superoxide-dismutase-activity-that-can-attenuate-oxidative-stress-on-endothelial-cells-induced-by-superoxide-anion
#16
Mengdi Wu, Kun Feng, Qiuhui Li, Huiya Ma, Hongli Zhu, Yudou Xie, Gaofei Yan, Chao Chen, Kunping Yan
A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH2-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn't show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals...
May 18, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28515175/role-for-reactive-oxygen-species-in-flow-stimulated-inner-medullary-collecting-duct-endothelin-1-production
#17
Will Wheatley, Donald E Kohan
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow and ET-1/GAPDH mRNA assessed. A shear stress of 10 dyne/cm2 for 1 hr increased ET-1 mRNA by 4-fold compared to no flow (ET-1 flow response)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28480509/oxidized-low-density-lipoprotein-stimulates-epithelial-sodium-channels-in-endothelial-cells-of-mouse-thoracic-aorta
#18
Chen Liang, Qiu-Shi Wang, Xu Yang, Na Niu, Qing-Qing Hu, Bao-Long Zhang, Ming-Ming Wu, Chang-Jiang Yu, Xiao Chen, Bin-Lin Song, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Epithelial sodium channel (ENaC) is expressed in endothelial cells and acts as a negative modulator of vasodilation. Oxidized low-density lipoprotein (ox-LDL) is a key pathological factor in endothelial dysfunction. The present study is to examine the role of ENaC in ox-LDL-induced endothelial dysfunction and its associated signal transduction pathway. EXPERIMENTAL APPROACH: Patch-clamp techniques combined with pharmacological approaches were used to examine ENaC activity in the endothelial cells of split-open mouse thoracic aorta...
May 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28467798/mechanism-of-oxidative-stress-p38mapk-sgk1-signaling-axis-in-experimental-autoimmune-encephalomyelitis-eae
#19
Liang Wang, Bin Li, Mo-Yuan Quan, Lin Li, Yuan Chen, Guo-Jun Tan, Jing Zhang, Xiao-Peng Liu, Li Guo
BACKGROUND: Multiple sclerosis (MS), a complex disease associated with multifocal demyelination of the central nervous system and poorly understood etiology. It has been previously indicated that many factors, including oxidative stress and p38MAPK-SGK1 pathway, contribute to the pathogenesis of MS. METHODS: This study, using an experimental autoimmune encephalomyelitis (EAE) model system, was aimed at investigating the molecular mechanisms determining interaction p38MAPK-SGK1 pathway and oxidative stress in MS pathogenesis...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459156/antioxidant-tempol-suppresses-heart-cytosolic-phospholipase-a2%C3%AE-stimulated-by-chronic-intermittent-hypoxia
#20
Petra Míčová, Martina Klevstig, Kristýna Holzerová, Marek Vecka, Jitka Žurmanová, Jan Neckář, František Kolář, Olga Nováková, Jiří Novotný, Markéta Hlaváčková
Adaptation to chronic intermittent hypoxia (CIH) is associated with reactive oxygen species (ROS) generation implicated in the improved cardiac tolerance against acute ischemia-reperfusion injury. Phospholipases A2 (PLA2s) play an important role in cardiomyocyte phospholipid metabolism influencing membrane homeostasis. Here we aimed to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA2 (cPLA2α), its phosphorylated form (p-cPLA2α), calcium-independent (iPLA2), and secretory (sPLA2IIA) at protein and mRNA levels, as well as fatty acids (FA) profile in left ventricular myocardium of adult male Wistar rats...
April 30, 2017: Canadian Journal of Physiology and Pharmacology
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