scholarly journals Asymmetric dimethylarginine (ADMA) accelerates cell senescence

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S65-S71 ◽  
Author(s):  
Stefanie M Bode-Böger ◽  
Fortunato Scalera ◽  
Jens Martens-Lobenhoffer
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Asymmetric Dimethylarginine ◽  
Telomerase Activity ◽  
Oxygen Free Radical ◽  
Cell Senescence ◽  
Slowing Down ◽  
Chemotactic Protein ◽  
Oxide Synthase

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and its accumulation has been associated with cardiovascular disease. We aimed to investigate the role of ADMA in endothelial cell senescence. Endothelial cells were cultured until the tenth passage. ADMA was replaced every 48 hours starting at the fourth passage. ADMA significantly accelerated senescence- associated β-galactosidase activity. Additionally, the shortening of telomere length was significantly speeded up and telomerase activity was significantly reduced. This effect was associated with an increase of oxidative stress: both allantoin, a marker of oxygen free radical generation, and intracellular reactive oxygen species increased significantly after ADMA treatment compared with control, whereas nitric oxide syn thesis decreased. Furthermore, ADMA-increased oxidative stress was accompanied by a decrease in the activity of dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA, which could be prevented by the antioxidant pyrroli dine dithiocarbamate. Exogenous ADMA also stimulated secretion of monocyte chemotactic protein-1 and interleukin-8. Co-incubation with the methyltransferase inhibitor S-adenosylhomocysteine abolished the effects of ADMA. These data suggest that ADMA accelerates senescence, probably via increased oxygen radical formation by inhibiting nitric oxide elaboration. This study provides evidence that modest changes of intracellular ADMA levels are associated with significant effects on slowing down endothelial senescence.

scholarly journals Asymmetric dimethylarginine (ADMA) accelerates cell senescence

2005 ◽  
Vol 10 (2_suppl) ◽  
pp. S65-S71 ◽  
Author(s):  
Stefanie M Bode-Böger ◽  
Fortunato Scalera ◽  
Jens Martens-Lobenhoffer
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Asymmetric Dimethylarginine ◽  
Telomerase Activity ◽  
Oxygen Free Radical ◽  
Cell Senescence ◽  
Slowing Down ◽  
Chemotactic Protein ◽  
Oxide Synthase

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and its accumulation has been associated with cardiovascular disease. We aimed to investigate the role of ADMA in endothelial cell senescence. Endothelial cells were cultured until the tenth passage. ADMA was replaced every 48 hours starting at the fourth passage. ADMA significantly accelerated senescence-associated β-galactosidase activity. Additionally, the shortening of telomere length was significantly speeded up and telomerase activity was significantly reduced. This effect was associated with an increase of oxidative stress: both allantoin, a marker of oxygen free radical generation, and intracellular reactive oxygen species increased significantly after ADMA treatment compared with control, whereas nitric oxide synthesis decreased. Furthermore, ADMA-increased oxidative stress was accompanied by a decrease in the activity of dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA, which could be prevented by the antioxidant pyrroli-dine dithiocarbamate. Exogenous ADMA also stimulated secretion of monocyte chemotactic protein-1 and interleukin-8. Co-incubation with the methyltransferase inhibitor S-adenosylhomocysteine abolished the effects of ADMA. These data suggest that ADMA accelerates senescence, probably via increased oxygen radical formation by inhibiting nitric oxide elaboration. This study provides evidence that modest changes of intracellular ADMA levels are associated with significant effects on slowing down endothelial senescence.

scholarly journals Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

2009 ◽  
Vol 296 (2) ◽  
pp. R195-R200 ◽  
Author(s):  
Dan Wang ◽  
Svend Strandgaard ◽  
Jens Iversen ◽  
Christopher S. Wilcox
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Essential Hypertension ◽  
Nitric Oxide Synthase ◽  
Plasma Levels ◽  
Asymmetric Dimethylarginine ◽  
Lipid Peroxidation Product ◽  
Individual Values ◽  
Oxide Synthase

We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension ( n = 9) compared with normal controls ( n = 10). We now test the hypothesis that the patients in this study have increased circulating levels of the cNOS inhibitor, asymmetric dimethylarginine (ADMA), or the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (HODE), which is a marker of reactive oxygen species. Patients had significantly ( P < 0.001) elevated (means ± SD) plasma levels of ADMA (PADMA, 766 ± 217 vs. 393 ± 57 nmol/l) and symmetric dimethylarginine (PSDMA: 644 ± 140 vs. 399 ± 70 nmol/l) but similar levels of l-arginine accompanied by significantly ( P < 0.015) increased rates of renal ADMA excretion (21 ± 9 vs. 14 ± 5 nmol/μmol creatinine) and decreased rates of renal ADMA clearance (18 ± 3 vs. 28 ± 5 ml/min). They had significantly increased plasma levels of HODE (PHODE: 309 ± 30 vs. 226 ± 24 nmol/l) and renal HODE excretion (433 ± 93 vs. 299 ± 67 nmol/μmol creatinine). For the combined group of normal and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly ( P < 0.001) and inversely correlated with microvascular EDRF/NO and positively correlated with mean blood pressure. In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure.

The Role of Nitric Oxide Synthase Inhibition by Asymmetric Dimethylarginine in the Pathophysiology of Preeclampsia

2010 ◽  
Vol 69 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Rainer H. B&ouml;ger ◽  
Anke Diemert ◽  
Edzard Schwedhelm ◽  
Nicole L&uuml;neburg ◽  
Renke Maas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Asymmetric Dimethylarginine ◽  
Oxide Synthase

scholarly journals 3-Nitrotyrosine in Sera of Patients with Myelodysplastic Syndromes, a Preliminary Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5624-5624
Author(s):  
Jaromir Novak ◽  
Jiri Suttnar ◽  
Leona Chrastinova ◽  
Jana Stikarova ◽  
Alzbeta Hlavackova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Czech Republic ◽  
Nitric Oxide Synthase ◽  
Myelodysplastic Syndromes ◽  
Asymmetric Dimethylarginine ◽  
Middle Age ◽  
Serum Samples ◽  
Healthy Donors ◽  
Oxide Synthase

Abstract Introduction: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoesis, associated with cytopenias and high risk of leukemic transformations with common morbidity. MDS are hematological malignancies of unclear etiology where oxidative/nitrative stress may contribute to the pathogenesis1. The posttranslational oxidative modifications of proteins and low molecular weight compounds are induced, revealing dysbalance of redox systems in vivo. Nitration of tyrosine either in free form or bound in proteins is important marker of nitric oxide synthase (NOS) activity shift in the presence of oxidative stress in favour of superoxide formation. The aim of this work was to assess whether 3-nitrotyrosine (3-NT) serum concentrations are enhanced also in MDS patients. Methods: Serum samples were obtained using blood of either MDS patients or healthy donors. All tested individuals agreed to the study at the time of blood collection. We proposed HPLC-MS/MS method to estimate 3-NT concentration in serum samples using QTRAP 4000 mass spectrometer (ABSciex, Prague, Czech Republic). Serum proteins were precipitated using ethanol, supernatants were evaporated, reconstituted in 0.1% HCOOH/2% methanol and injected onto HALO C18 microcolumn 100x0.5 mm (ABSciex, Prague, Czech Republic). Oxidative stress in MDS patients and controls was assessed by serum malondialdehyde concentrations measured by HPLC of 2-thiobarbituric acid MDA derivative using UV detection. Results: The sensitivity of method proposed for analysis of 3-NT in sera was sufficient for estimation of differences of 3-NT in patients and control samples. We have found enhanced concentrations of both MDA and 3-nitrotyrosine in serum of MDS patients as compared with healthy donors. Discussion: Enhanced MDA concentrations in MDS patients confirmed the presence of oxidative stress in MDS patients. The reactive oxygen species may oxidize tetrahydrobiopterin, important cofactor of NOS, resulting into nitric oxide synthase uncoupling with enhanced superoxide and consequently peroxynitrite production2. It is known that methylarginines, naturally occurring inhibitors of NOS, can profoundly increase superoxide generation from uncoupled NOS. Recently, we have found significantly enhanced concentration of asymmetric dimethylarginine in a serum of middle age patients with myelodysplastic syndrome3. The observed increased concentrations of 3-NT in MDS patients correspond with assumed enhanced peroxynitrite formation as compared with controls. 3-nitrotyrosine concentrations thus could serve as a new criterion of NOS changed activity in MDS patients. Literature: 1. Farquhar MJ, Bowen DT. Oxidative stress and the myelodysplastic syndromes. Int J Hematol. 2003;77:342-350. 2. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87:315-424. 3. Štikarová J, Suttnar J, Pimková K, Chrastinová-Mášová L, Čermák J, Dyr JE. Enhanced levels of asymmetric dimethylarginine in a serum of middle age patients with myelodysplastic syndrome. Journal of Hematology & Oncology. 2013;6:58. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nitric Oxide Bioavailability in Obstructive Sleep Apnea: Interplay of Asymmetric Dimethylarginine and Free Radicals

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammad Badran ◽  
Saeid Golbidi ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Endothelial Function ◽  
Asymmetric Dimethylarginine ◽  
Critical Role ◽  
Middle Aged ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men and is considered an independent risk factor for cerebrovascular and cardiovascular diseases. Nitric oxide (NO) is an important endothelium derived vasodilating substance that plays a critical role in maintaining vascular homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in the human circulation. Elevated levels of ADMA inhibit NO synthesis while oxidative stress decreases its bioavailability, so impairing endothelial function and promoting atherosclerosis. Several clinical trials report increased oxidative stress and ADMA levels in patients with OSA. This review discusses the role of oxidative stress and increased ADMA levels in cardiovascular disease resulting from OSA.

scholarly journals A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Shuhua ◽  
Liu Ziyou ◽  
Yan Ling ◽  
Wang Fei ◽  
Guifan Sun
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Dependent Manner ◽  
Microglia Cell ◽  
The Central Nervous System ◽  
Radical Generation ◽  
Oxide Synthase ◽  
Cell Medium ◽  
Dose Dependent

The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions (O2∙-), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS andO2∙-increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

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