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Arginine methylation macrophage

Nicholas S Kirkby, Abel Tesfai, Blerina Ahmetaj-Shala, Hime H Gashaw, Walkyria Sampaio, Gisele Etelvino, Nádia Miricéia Leão, Robson A Santos, Jane A Mitchell
Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their antiinflammatory effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused by blocking COX-2 in the vasculature and/or kidney, with our recent work implicating the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose effects can be prevented by l-arginine. The ibuprofen salt ibuprofen arginate (Spididol) was created to increase solubility but we suggest that it could also augment the NO pathway through codelivery of arginine...
September 6, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jiamei Shen, Adam Hafeez, James Stevenson, Jianjie Yang, Changbin Yin, Fengwu Li, Sainan Wang, Huishan Du, Xunming Ji, Jose A Rafols, Xiaokun Geng, Yuchuan Ding
OBJECTIVES: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks...
August 11, 2016: Neuroscience
Yusaku Mori, Simon Chiang, Michelle P Bendeck, Adria Giacca
It has been argued whether insulin accelerates or prevents atherosclerosis. Although results from in vitro studies have been conflicting, recent in vivo mice studies demonstrated antiatherogenic effects of insulin. Insulin is a known activator of endothelial nitric oxide synthase (NOS), leading to increased production of NO, which has potent antiatherogenic effects. We aimed to examine the role of NOS in the protective effects of insulin against atherosclerosis. Male apolipoprotein E-null mice (8 wk old) fed a high-cholesterol diet (1...
August 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Hui-Chen Lo, Ching-Yi Hung, Fu-Huan Huang, Tzu-Cheng Su, Chien-Hsing Lee
The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days...
2016: PloS One
Hana A Itani, Liang Xiao, Mohamed A Saleh, Jing Wu, Mark A Pilkinton, Bethany L Dale, Natalia R Barbaro, Jason D Foss, Annet Kirabo, Kim R Montaniel, Allison E Norlander, Wei Chen, Ryosuke Sato, L Gabriel Navar, Simon A Mallal, Meena S Madhur, Kenneth E Bernstein, David G Harrison
RATIONALE: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. OBJECTIVE: To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. METHODS AND RESULTS: We imposed repeated hypertensive challenges using either N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice...
April 15, 2016: Circulation Research
S An, G Zong, Z Wang, J Shi, H Du, J Hu
BACKGROUND: Nitric oxide (NO) and mast cells (MCs) are possibly involved in the development of irritable bowel syndrome (IBS), but details on their role and interactions still remain undetermined. We aimed to investigate the expression of inducible NO synthase (iNOS) in MCs of the colon of IBS with diarrhea (IBS-D), and elucidated a potential role of NO in the differential regulation of cytokines in MCs. METHODS: Colonic mucosal biopsies of 19 IBS-D patients and 16 healthy controls were collected...
July 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Yinpu Yue, Wei Huang, Jingjing Liang, Jing Guo, Jian Ji, Yunliang Yao, Mingzhu Zheng, Zhijian Cai, Linrong Lu, Jianli Wang
Interleukin 4-induced gene-1 (IL4I1) was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ) expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM) differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns...
2015: PloS One
Imtiyaz Yaseen, Prabhjot Kaur, Vinay Kumar Nandicoori, Sanjeev Khosla
Mycobacteria are successful pathogens that modulate the host immune response through unclear mechanisms. Here we show that Rv1988, a secreted mycobacterial protein, is a functional methyltransferase that localizes to the host nucleus and interacts with chromatin. Rv1988 methylates histone H3 at H3R42 and represses the genes involved in the first line of defence against mycobacteria. H3R42me2, a non-tail histone modification, is present at the entry and exit point of DNA in the nucleosome and not within the regulatory sites in the N-terminal tail...
2015: Nature Communications
Lauren A Biwer, Karen M D'souza, Ali Abidali, Danni Tu, Ashley L Siniard, Matthew DeBoth, Matthew Huentelman, Taben M Hale
We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (L-arginine methyl ester, L-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects...
January 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Wei He, Peter Zhou, Zhigang Chang, Baoling Liu, Xuefeng Liu, Yanming Wang, Yongqing Li, Hasan B Alam
BACKGROUND: We have recently shown that inhibition of peptidylarginine deiminase (PAD) improves survival in a rodent model of lethal cecal ligation and puncture. The roles of PAD inhibitors in hemorrhagic shock (HS), however, are largely unknown. The goal of this study was to investigate the effects of YW3-56, a novel PAD inhibitor, on survival after severe HS. METHODS: Mouse macrophages were exposed to hypoxic conditions followed by reoxygenation in the presence or absence of YW3-56...
February 2016: Journal of Surgical Research
K M D'Souza, L A Biwer, L Madhavpeddi, P Ramaiah, W Shahid, T M Hale
Transient angiotensin-converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitor-induced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHRs) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 wk followed by a 2-wk washout period and a subsequent 7-day challenge with the NOS inhibitor N(ω)-nitro-l-arginine methyl ester...
October 2015: American Journal of Physiology. Heart and Circulatory Physiology
Sonia André, Shannon K Washington, Emily Darby, Marvin M Vega, Ari D Filip, Nathaniel S Ash, Katy A Muzikar, Christophe Piesse, Thierry Foulon, Daniel J O'Leary, Ali Ladram
Short antimicrobial peptides represent attractive compounds for the development of new antibiotic agents. Previously, we identified an ultrashort hydrophobic and phenylalanine-rich peptide, called temporin-SHf, representing the smallest natural amphibian antimicrobial peptide known to date. Here, we report on the first structure-activity relationship study of this peptide. A series of temporin-SHf derivatives containing insertion of a basic arginine residue as well as residues containing neutral hydrophilic (serine and α-hydroxymethylserine) and hydrophobic (α-methyl phenylalanine and p-(t)butyl phenylalanine) groups were designed to improve the antimicrobial activity, and their α-helical structure was investigated by circular dichroism and nuclear magnetic resonance spectroscopy...
October 16, 2015: ACS Chemical Biology
Eric Adua, Frank Oteng Danso, Oswald Mensah Boa-Amponsem, Frank Adusei-Mensah
BACKGROUND: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. OBJECTIVE: To investigate whether the entry of neutrophils and release of arginase can interfere with nitric oxide production from stimulated mouse macrophages...
June 2015: Iranian Journal of Immunology: IJI
Bhagawat S Chandrasekar, Shikha Yadav, Emmanuel S Victor, Shamik Majumdar, Mukta Deobagkar-Lele, Nitin Wadhwa, Santosh Podder, Mrinmoy Das, Dipankar Nandi
Interferon-gamma (Ifnγ), a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifnγ to induce the aggregation of resident mouse adherent peritoneal exudate cells (APECs), consisting primarily of macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition of Ifnγ, CD11b re-localizes preferentially to the sites of interaction on APECs. A functional role of CD11b in enhancing aggregation is demonstrated using Reopro, a blocking reagent, and siRNA to Cd11b...
2015: PloS One
Lisa A Ridnour, Robert Y S Cheng, Jonathan M Weiss, Sukhbir Kaur, David R Soto-Pantoja, Debashree Basudhar, Julie L Heinecke, C Andrew Stewart, William DeGraff, Anastasia L Sowers, Angela Thetford, Aparna H Kesarwala, David D Roberts, Howard A Young, James B Mitchell, Giorgio Trinchieri, Robert H Wiltrout, David A Wink
Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME)...
July 15, 2015: Cancer Research
Yuexia Zhang, Zhenhua Yang, Yan Feng, Ruijin Li, Quanxi Zhang, Hong Geng, Chuan Dong
The main aim of the present study was to examine in vitro responses of rat alveolar macrophages (AMs) exposed to coarse chalk dust particles (particulate matter in the size range 2.5-10 μm, PM(coarse)) by respiratory burst and oxidative stress. Chalk PM(coarse)-induced respiratory burst in AMs was measured by using a luminol-dependent chemiluminescence (CL) method. Also, the cell viability; lactate dehydrogenase (LDH) release; levels of cellular superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and acid phosphatase (ACP); plasma membrane ATPase; and extracellular nitric oxide (NO) level were determined 4 h following the treatment with the different dosages of chalk PM(coarse)...
August 2015: Environmental Science and Pollution Research International
Takaichi Suehiro, Kazuhiko Tsuruya, Hirofumi Ikeda, Jiro Toyonaga, Shunsuke Yamada, Hideko Noguchi, Masanori Tokumoto, Takanari Kitazono
Chronic inhibition of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester (L-NAME) causes progressive renal injury and systemic hypertension. Angiotensin II (Ang II) has been conventionally regarded as one of the primary causes of renal injury. We reported previously that such renal injury was almost completely suppressed by both an Ang II type I receptor blocker and an aldosterone antagonist. The aldosterone antagonist also inhibited the systemic Ang II elevation. Therefore, it remains to be elucidated whether Ang II or aldosterone directly affects the development of such renal injury...
July 2015: Endocrinology
Atsushi Koike, Isato Minamiguchi, Ko Fujimori, Fumio Amano
Heme oxygenase-1 (HO-1) catabolizes the degradation of heme into bilirubin, carbon monoxide, and iron ions. The HO-1 products provide antioxidant cytoprotection in addition to having potent antiinflammatory and immunomodulatory functions. HO-1 is induced by its substrate heme and environmental factors including oxidative and heat stresses. Although previous studies reported that lipopolysaccharide (LPS) induced the expression of both the HO-1 gene and its protein in macrophages, the major regulators of HO-1 expression remain unknown...
2015: Biological & Pharmaceutical Bulletin
J Rincón, D Correia, J L Arcaya, E Finol, A Fernández, M Pérez, K Yaguas, E Talavera, M Chávez, R Summer, F Romero
AIMS: Activation of the renin-angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with N(w)-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown...
March 1, 2015: Life Sciences
Ryan D Sheldon, Jaume Padilla, Nathan T Jenkins, M Harold Laughlin, R Scott Rector
The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (NOS) via N(ω)-nitro-L-arginine methyl ester (L-NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats received control or L-NAME (65-70 mg·kg(-1)·day(-1))-containing drinking water for 4 wk...
March 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
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