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DDAH/ADMA pathway

Nandini Nair, Enrique Gongora
BACKGROUND The concept of antioxidant therapies assumes high importance as oxidative stress is associated with cardiovascular aging via endothelial dysfunction. This review focusses on exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular function. OBJECTIVE A systematic review of literature from 1990 to 2016 was conducted using Pubmed and Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of DDAH I which degrades ADMA , the endogenous inhibitor of nitric oxide synthase ...
February 16, 2017: Current Cardiology Reviews
Kai Cui, Yang Luan, Zhe Tang, Ke Rao, Tao Wang, Zhong Chen, Shaogang Wang, Jihong Liu, Daowen Wang
Our previous studies had reported that Human Tissue Kallikrein 1 (hKLK1) preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into four groups: young WTR (yWTR) as the control, aged WTR (aWTR), aged TGR (aTGR) and aged TGRs with HOE140 (aTGRH)...
2017: PloS One
Ru Zhou, Ping Ma, Aiqin Xiong, Yehua Xu, Yang Wang, Qingbin Xu
AIMS: Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms. METHODS: Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection...
April 2017: Cardiovascular Therapeutics
Ru Zhou, Qingbin Xu, Yehua Xu, Aiqin Xiong, Yang Wang, Ping Ma
Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nicole Lüneburg, Patricia Siques, Julio Brito, Karem Arriaza, Eduardo Pena, Hans Klose, Fabiola Leon-Velarde, Rainer H Böger
Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days...
2016: Pulmonary Medicine
Begoña Quintana-Villamandos, Ana Arnalich-Montiel, Silvia Arribas, Nicole Lüneburg, Rainer H Böger, María Jesús Delgado-Martos, Carmen Fernández-Criado, Emilio Delgado-Baeza, María Carmen González
Our preclinical study demonstrated that esmolol produces early regression of left ventricular hypertrophy in arterial hypertension. The aim of this study was to assess the effects of short-term esmolol therapy on the regression of left anterior descending artery remodeling in spontaneously hypertensive rats (SHRs), and to determine whether the asymmetric dimethylarginine (ADMA)/dimethylarginine dimethylaminohydrolase (DDAH) pathway, a regulator of nitric oxide (NO) bioavailability, accounted for this regression...
October 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Rhys B Murphy, Sara Tommasi, Benjamin C Lewis, Arduino A Mangoni
Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO) production, mediated via its biochemical interaction with the nitric oxide synthase (NOS) family of enzymes...
May 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Dong Chen, Ke-Qin Zhang, Bo Li, Ding-Qi Sun, Hui Zhang, Qiang Fu
Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg-1 and 100 mg kg-1 for 12 weeks, respectively...
April 15, 2016: Asian Journal of Andrology
Li Lai, Yohannes T Ghebremariam
Insulin resistance syndrome (IRS) is a configuration of cardiovascular risk factors involved in the development of metabolic disorders including type 2 diabetes mellitus. In addition to diet, age, socioeconomic, and environmental factors, genetic factors that impair insulin signaling are centrally involved in the development and exacerbation of IRS. Genetic and pharmacological studies have demonstrated that the nitric oxide (NO) synthase (NOS) genes are critically involved in the regulation of insulin-mediated glucose disposal...
2016: Journal of Diabetes Research
Hong-Bo Xiao, Zi-Kui Liu, Xiang-Yang Lu, Chun-Na Deng, Zhi-Feng Luo
BACKGROUND: Oxidative stress may affect PRMT/ADMA/DDAH (protein arginine methyltransferases/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase) pathway to impair endothelial dysfunction. The present study was carried out to test the effect of icariin on endothelial function and the mechanisms responsible for this. METHODS: Eighty mice at 12 weeks of age were separated randomly into four groups (n = 20): C57BL/6J control, untreated apolipoprotein E-deficient (ApoE(-/-)), two groups of icariin-treated (10 or 30 mg/kg body wt/day, intragastrically) ApoE(-/-)...
December 2015: Pharmacological Reports: PR
Shiro Mizuno, Takeshi Ishizaki, Hirohisa Toga, Akio Sakai, Jainagul Isakova, Elnura Taalaibekova, Zamirbek Baiserkeev, Baktybek Kojonazarov, Almaz Aldashev
Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks...
2015: BioMed Research International
Rossella Menghini, Viviana Casagrande, Marina Cardellini, Marta Ballanti, Francesca Davato, Iris Cardolini, Robert Stoehr, Marta Fabrizi, Monica Morelli, Lucia Anemona, Isabel Bernges, Edzard Schwedhelm, Arnaldo Ippoliti, Alessandro Mauriello, Rainer H Böger, Massimo Federici
BACKGROUND AND AIMS: The O subfamily of forkhead (FoxO) 1 is a pivotal element in the regulation of endothelial activation. Compartmentalization and activity of FoxO1 is regulated by post translational modifications, but the implication in endothelial dysfunction and atherosclerosis remain controversial. Our aim was to identify FoxO1 related metabolic signatures in endothelial cells. METHODS AND RESULTS: Using metabolomics in human umbilical endothelial cells (HUVECs) overexpressing the wild type FoxO1 (FoxO1-WT), the acetylation defective mutant (FoxO1-KR), the unphosphorylated nuclear localized mutant (FoxO1-ADA) and the Green Fluorescent Protein (GFP) control vector, we identify metabolic pathways differentially affected by the different FoxO1 localization and activity...
September 2015: Atherosclerosis
B A Lumicisi, J E Cartwright, K Leslie, A E Wallace, G S Whitley
STUDY QUESTION: Does inhibition of dimethylarginine dimethylaminohydrolase (DDAH) increase the sensitivity of trophoblasts to TRAIL-induced apoptosis? SUMMARY ANSWER: Inhibition of DDAH1, but not DDAH2, increases the sensitivity of trophoblasts to TRAIL-induced apoptosis. WHAT IS KNOWN ALREADY: Successful human pregnancy is dependent on adequate trophoblast invasion and remodelling of the maternal spiral arteries. Increased trophoblast apoptosis is seen in pregnancies complicated by pre-eclampsia...
August 2015: Human Reproduction
J-H Wang, D Chen, K-Q Zhang, H Zhang, Q Fu
The effect of DDAH/ADMA/NOS pathway in penile tissue of rats of different age was investigated to better understand the mechanism of age-related erectile dysfunction (ED). The Sprague Dawley male rats were assigned as the young group (3 month old, n = 10) and the old group (18 month old, n = 10) respectively. Intracavernous pressure (ICP) was measured before and after papaverine intracavernous injection. Pathology structure of penile tissue was evaluated under transmission electron microscope. The expression amounts of asymmetric dimethylarginine (ADMA) and cyclic guanosine monophosphate (cGMP) in penile tissue were detected by ELISA; the expression levels of isoform-specific DDAH and NOS were assessed via Western blot...
April 2016: Andrologia
Elizabeth B Staab, Jason Weigel, Fengxia Xiao, Nandakumar Madayiputhiya, Todd A Wyatt, Sandra M Wells
There is increasing evidence that the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethyl-arginine (ADMA) is involved in the pathogenesis of chronic lung diseases. One important regulator of this molecule is the ADMA-metabolizing enzyme dimethyl-arginine dimethyl-aminohydrolase (DDAH). The objective of this study was to determine whether perturbation of the ADMA-DDAH pathway contributes to lung inflammation following exposure to cigarette smoke (CS). For these studies, wild-type and DDAH transgenic mice were sham or CS-exposed...
July 2015: Journal of Immunotoxicology
Zhen Zhong Zheng, Xiao Tian Fu, Jin Liang, Zhi Bing Guo
BACKGROUND: Cardiotrophin-1 (CT-1), a member of the IL-6 superfamily, is elevated in the serum of patients with ischemic and valvular heart disease. In this study, we hypothesized that CT-1 induces endothelial cell angiogenesis and that the ADMA/DDAH pathway plays an important role in the process. METHODS: pEGFP-N1-CTF1-GFP and pEGFP-N1 were constructed and used to transiently transfect to HUVECs, mediated by LipofectamineTM 2000. After transfection, the expression of CT-1 was examined by qRT-PCR and western blotting...
December 2015: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Qiong Yuan, Chang-Ping Hu, Zhi-Cheng Gong, Yong-Ping Bai, Si-Yu Liu, Yuan-Jian Li, Jun-Lin Jiang
The risk of cardiovascular complications in diabetic patients is mainly associated with endothelial dysfunction. Reduced number of EPCs and impaired function of EPCs in diabetes result in imbalance of endothelial homeostasis and dysfunction of vessels. In patients with diabetes mellitus, plasma levels of asymmetric dimethylarginine (ADMA) were elevated, while the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) were reduced. In the present study, we investigated the role of the DDAH2/ADMA pathway in the senescence of EPCs in type 2 diabetic patients and cultured EPCs treated with high glucose...
March 20, 2015: Biochemical and Biophysical Research Communications
Krzysztof Milewski, Wojciech Hilgier, Jan Albrecht, Magdalena Zielińska
Hepatic encephalopathy (HE) is related to variations in the nitric oxide (NO) synthesis and oxidative/nitrosative stress (ONS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOSs). In the present study we compared the effects of acute liver failure (ALF) in the rat TAA model on ADMA concentration in plasma and cerebral cortex, and on the activity and expression of the ADMA degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), in brain and liver. ALF increased blood and brain ADMA, and the increase was correlated with decreased DDAH activity in both brain and liver...
September 2015: Neurochemistry International
Wei Zhang, Jian Zhang, Yansheng Kang Liu, Jingjing Liu, Xiaoqing Wang, Qingbin Xu, Yilei Wang, Xiaoya Xu, Guidong Dai
The present study was designed to investigate whether oxymatrine could attenuate isoproterenol-induced heart failure via regulation of asymmetric dimethylarginine (ADMA) metabolism in rats. Heart failure model was established by once daily subcutaneous injection of isoproterenol (5 mg/kg/d) to rats for 7 days. Simultaneously, oral administration of oxymatrine (25, 50 and 100 mg/kg/d) was started from day 1 to day 7, or with vehicle as corresponding controls. After continuous preventive administration of oxymatrine for 7 days, significant isoproterenol-induced heart failure characterized by hypertrophy and dysfunction of left ventricle, and elevation of brain natruretic peptide (BNP, a heart failure biomarker) and cardiac troponin I (cTn-I, a cardiac injury biomarker) was observed...
December 15, 2014: European Journal of Pharmacology
Andrea Ferrigno, Vittoria Rizzo, Alberto Bianchi, Laura G Di Pasqua, Clarissa Berardo, Plinio Richelmi, Mariapia Vairetti
We investigated the effects of hepatic ischemia/reperfusion (I/R) injury on asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (involved, resp., in ADMA synthesis and degradation), and the cationic transporter (CAT). Male Wistar rats were subjected to 30 or 60 min hepatic ischemia followed by 60 min reperfusion. ADMA levels in serum and bile were determined. Tissue ADMA, DDAH activity, DDAH-1 and CAT-2 protein, DDAH-1 and PRMT-1 mRNA expression, GSH/GSSG, ROS production, and lipid peroxidation were detected...
2014: BioMed Research International
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