DDAH/ADMA pathway

BACKGROUND: Contrast medium-induced acute kidney injury (CI-AKI) is one of the most common causes of hospital-acquired acute renal failure. However, the pathogenesis of CI-AKI remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor that is largely metabolised by dimethylarginine dimethylaminohydroxylase (DDAH) in humans. Two isoforms of DDAH exist, namely, DDAH-1 and DDAH-2. In the present study, we examined whether the DDAH-2/ADMA/NOS pathway is involved in the pathogenesis of CI-AKI...

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS). ADMA is degraded by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of ADMA lead to reduction in nitric oxide (NO) production, which is linked to endothelial dysfunction and atherosclerosis. Piper sarmentosum is an herb that has shown stimulation on endothelial NO production by increasing both expression and activity of eNOS. Thus, this study determined whether the positive effect of P...

BACKGROUND: Proton pump inhibitors (PPIs) are frequently used to prevent or treat peptic ulcers. Recently, PPIs have been shown to increase the risk of myocardial infarction. The purpose of this study was to determine whether PPIs adversely affect ventricular remodeling in infarcted rats. METHODS: Male Wistar rats were randomly assigned to receive either vehicle, omeprazole, omeprazole + vitamin C, omeprazole + olmesartan, or famotidine treatment for 4 weeks starting 24 hours after inducing myocardial infarction by ligating coronary arteries...

Recent studies show that nitric oxide/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase (NO/ADMA/DDAH) pathway may contribute to the development of sleep disorder. The objective of this study was to explore the inhibitory effect of procyanidin B2 from lotus seedpod (LSPC), a naturally occurring catechin compound, on insomnia and the mechanisms involved. The experiments were performed in brain from Sprague-Dawley rat control and insomniac rats treated or not with LSPC (15, 30, and 45 mg/kg, intragastrically) for 7 days...

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a key enzyme involved in the metabolism of the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA). Increased DDAH1 expression and subsequent increased NO production have been recently linked to cancer. Specifically, DDAH1 is implicated in establishment of a vascular network by tumour cells, vasculogenic mimicry (VM), which is strongly associated with tumour progression and poor patient prognosis...

BACKGROUND: Although fruit and vegetable-rich diets have beneficial effects on cardiovascular diseases, we have little knowledge of the impact of fruits and their constituents, iridoids and anthocyanins, on the l-arginine-ADMA-DDAH pathway. Our previous study demonstrated the modulation of those factors by the oral administration of the cornelian cherry fruit. HYPOTHESIS/PURPOSE: We have assessed the effects of the oral administration of two main constituents isolated from the cornelian cherry fruit, iridoid loganic acid and anthocyanins, on l-arginine, its derivatives (ADMA, SDMA), metabolites (DMA, l-citrulline), and the hepatic DDAH activity and its isoform expression in rabbits fed a high-cholesterol diet...

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension‑independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl‑L‑arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway...

BACKGROUND: Diabetic erectile dysfunction (DMED) is mainly attributed to oxidative stress, and Nrf2 plays an important role in cellular antioxidation and regulates NO production in the vascular endothelium. Probucol maintains endothelial function through its antioxidant activity. This study investigated the efficacy and mechanism of probucol in improving erectile function in streptozotocin-induced diabetic rats. METHODS: In our study, thirty 12-week-old Sprague-Dawley male rats were fasted for 12 h...

BACKGROUND: A correlation between the level of asymmetric dimethylarginine (ADMA) - the inhibitor of the nitric oxide (NO) synthesis - and the liver function and survival after a liver transplantation has been reported. OBJECTIVES: The aim of this study was to evaluate the effect of sitagliptin -the inhibitor of dipeptidyl peptidase-4 (DPP-4) - on the NO-ADMA-dimethylarginine dimethylaminohydrolase (DDAH) pathway in rat livers subjected to ischemia/reperfusion (IR)...

AIM OF THE STUDY: The lung architecture of newborns appears to be affected by an inflammatory reaction to maternal choriodecidual layer infection. L-citrulline (L-Cit) was administered to pregnant rats exposed to intra-amniotic lipopolysaccharide (LPS)-induced chorioamnionitis to investigate its effect on neonatal lung injury. MATERIALS AND METHODS: The pups were assigned to four experimental groups: 1- pups exposed to intra-amniotic NaCl but not to postnatal L-Cit (Controls); 2 - pups exposed to intra-amniotic NaCl as well as to postnatal L-Cit treatment (L-Cit group); 3 - pups exposed to prenatal LPS but not to postnatal (LPS); 4- pups exposed to prenatal LPS as well as to postnatal L-Cit treatment (LPS + L-Cit)...

BACKGROUND: To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model. METHODS: 2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups...

The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated...

There are animal species that have adapted to life at high altitude and hypobaric hypoxia conditions in the Andean highlands. One such species is the llama ( Lama glama ), which seem to have developed efficient protective mechanisms to avoid maladaptation resulting from chronic hypoxia, such as a resistance to the development of hypoxia -induced pulmonary hypertension. On the other hand, it is widely known that different models of hypertension can arise as a result of changes in endothelial function. The respect, one of the common causes of deregulation in endothelial vasodilator function have been associated with down-regulation of the NO synthesis and an increase in plasma levels of asymmetric dimethylarginine (ADMA) and homocysteine...

Asymmetric dimethylarginine (ADMA) is a risk factor for heart diseases. Dimethylarginine dimethylaminohydrolase (DDAH) enzymes are key proteins for ADMA degradation. Endothelial DDAH1 is a vital regulator of angiogenesis. DDAH1 is also expressed in cardiomyocytes. However, the role of DDAH1 in cardiomyocytes needs further clarification. Herein, we used an inducible cardiac-specific DDAH1 knockdown mouse (cardiac DDAH1-/- ) to investigate the role of cardiomyocyte DDAH1 in left-ventricular (LV) remodeling after acute myocardial infarction (AMI)...

Diabetic retinopathy (DR) is a leading cause of vision loss with retinal neovascularization. This study aims to investigate whether Asymmetric dimethylarginine (ADMA) impacts the pathogenesis of DR via focusing on promoting retinal neovascularization and its underlying molecular mechanisms. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) for 20 weeks. ADMA levels in aqueous and the influence of hypoxia on ADMA and angiogenesis in RF/6A cells were examined. The effects and underlying molecular mechanisms of ADMA on neovascularization of RF/6A cells were further evaluated by administration of ADMA, DDAH siRNA or ephrinB2 siRNA...

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA)...

Asymmetric dimethylarginine (ADMA) is catalyzed by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) in humans, and the role for ADMA has been associated with hepatic fibrogenesis. Transforming growth factor‑β (TGF‑β) has been shown to mediate the myofibroblastic transformation of quiescent hepatic stellate cells (HSCs), a pivotal step in liver fibrogenesis. However, the underlying molecular mechanisms are not well understood. Accumulation of ADMA due to low activity of DDAH has been reported to be associated with liver damage and hepatic fibrosis...

Tissue microarray analysis confirmed higher dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression in prostate cancer (PCa) compared to benign and normal prostate tissues. DDAH1 regulates nitric oxide (NO) production by degrading endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA). This study examined whether DDAH1 has any physiological role in PCa progression. Using overexpression of DDAH1 in PCa (PC3 and LNCaP) cell lines, we found that DDAH1 promotes cell proliferation, migration and invasion by lowering ADMA levels, as well as increasing NO production...

BACKGROUND: Anti-angiogenic therapies, targeting VEGF, are a promising treatment for hepatocellular carcinoma (HCC). To enhance this potential therapy, identification of novel targets in this pathway is of major interest. Nitric oxide (NO) plays a crucial role in VEGF-dependent angiogenesis. NO production depends on arginine as substrate and asymmetric dimethylarginine (ADMA) as inhibitor. Dimethylarginine dimethylaminohydrolase 1 (DDAH-1) catabolizes ADMA and therefore regulates NO and VEGF expression...

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH])...