DDAH/ADMA pathway

MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort...

Our investigation intended to analyze the effects of sulfated polysaccharides from Caulerpa racemosa (SPCr) in attenuating obesity-induced cardiometabolic syndrome via regulating the protein arginine N-methyltransferase 1-asymmetric dimethylarginine-dimethylarginine dimethylamino-hydrolase (PRMT1-DDAH-ADMA) with the mammalian target of rapamycin-Sirtuin 1-5' AMP-activated protein kinase (mTOR-SIRT1-AMPK) pathways and gut microbiota modulation. This is a follow-up study that used SPs from previous in vitro studies, consisting of 2,3-di- O -methyl-1,4,5-tri- O -acetylarabinitol, 2,3,4,6-tetra- O -methyl-D-mannopyranose, and type B ulvanobiuronicacid 3-sulfate...

This study evaluated the effects of an aqueous extract of Caulerpa racemosa (AEC) on cardiometabolic syndrome markers, and the modulation of the gut microbiome in mice administered a cholesterol- and fat-enriched diet (CFED). Four groups of mice received different treatments: normal diet, CFED, and CFED added with AEC extract at 65 and 130 mg/kg body weight (BW). The effective concentration (EC50 ) values of AEC for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and lipase inhibition were lower than those of the controls in vitro...

The enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a pivotal role in the regulation of nitric oxide levels by degrading the main endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Growing evidence highlight the potential implication of DDAH/ADMA axis in the etiopathogenesis of several neuropsychiatric and neurological disorders, yet the underlying molecular mechanisms remain elusive. In this study, we sought to investigate the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance...

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil...

Nitric oxide synthase- (NOS-) dependent endothelial dysfunction induced by oxidative stress (OS) is assumed to play a pivotal role in the pathogenesis and progression of diabetes mellitus-related erectile dysfunction (DMED). Cysteine-rich whey protein isolate (CR-WPI) is a widely used protein supplement and has been confirmed to reduce reactive oxygen species (ROS) by increasing cellular antioxidant glutathione (GSH). However, it is currently unknown whether CR-WPI elicits therapeutic effects in DMED. Here, we provide diabetic rats with CR-WPI to determine its effect on DMED and the underlying mechanisms...

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear...

High serum levels of asymmetric dimethyl arginine (ADMA) are associated with cardiovascular disease and mortality. Pharmacological agents to specifically lower ADMA and their potential impact on cardiovascular complications are not known. In this study, we aimed to investigate the effect of specific lowering of ADMA on myocardial response to ischemia-reperfusion injury (I/R) and direct effects on cardiomyocyte function. Effects of recombinant dimethylarginine dimethylaminohydrolase (rDDAH)-1 on I/R injury were determined using isolated mouse heart preparation...

Chronic intermittent hypoxia leads to high-altitude pulmonary hypertension, which is associated with high asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis. Therefore, we aimed to understand the relation of single nucleotide polymorphisms in this pathway to high-altitude pulmonary hypertension (HAPH). We genotyped 69 healthy male Chileans subjected to chronic intermittent hypoxia. Acclimatization to altitude was determined using the Lake Louise Score and the presence of acute mountain sickness...

OBJECTIVE: To investigate whether icariin improves erectile function in spontaneously hypertensive rats (SHR) by regulating the NRF2 pathway. METHODS: We equally randomized 24 ten-week-old healthy male Wistar-Kyoto rats (WKR) and healthy male SHR rats into four groups: WKR control, WKR + icariin, SHR control and SHR + icariin, the controls treated intragastrically with normal saline, and the animals in the WKR + icariin and SHR + icariin groups with icariin, all at 10 mg/kg/d for 4 weeks...

Hyperuricemia is closely associated with the mobility and mortality of patients with cardiovascular diseases. However, how hyperuricemia accelerates atherosclerosis progression is not well understood. The balance between asymmetric dimethylarginine (ADMA) and dimethylarginine dimethylaminotransferases (DDAHs) is crucial to regulate vascular homeostasis. Therefore, we investigated the role of the ADMA/DDAH pathway in hyperuricemia-induced endothelial dysfunction and atherosclerosis and the underlying molecular mechanisms in endothelial cells (ECs) and apolipoprotein E-knockout (apoe-/- ) mice...

Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7th day, 1 h after perindopril administration. Pantoprazole was used as a standard agent...

STUDY OBJECTIVE: Long-term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA...

The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet...

Background: The incidence of metabolic syndrome is increasing worldwide and this is mainly attributed to high carbohydrate intake, especially of fructose, and sedentary lifestyles. Nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS) enzymes, is a crucial molecule for endothelial and renal health. Asymmetric dimethylarginine (ADMA) is the most potent inhibitor of NOS and it is degraded by dimethylarginine dimethylaminohydrolase (DDAH). The aim of this study was to investigate the effects of melatonin on renal NO-ADMA metabolism using a metabolic syndrome model achieved by fructose administration...

Asymmetric protein-arginine dimethylation is a major post-translational modification (PTM) catalyzed by protein-arginine methyltransferase (PRMT). Regular proteolysis releases asymmetric dimethylarginine (ADMA). Of the daily produced ADMA, about 10% are excreted unchanged in the urine. The remaining 90% are hydrolyzed by dimethylarginine dimethylaminohydrolase (DDAH) to L-citrulline and dimethylamine (DMA), which is readily excreted in the urine. The PRMT/DDAH pathway is almost the exclusive origin of urinary ADMA and the major source of urinary DMA...

Kaempferol (Kae), a flavonoid, has been found in fruits and other vegetables, possesses many biological activities. 14-3-3 protein exerts protection on various types of injured tissues and cells. Doxorubicin (Dox) causes excessive reactive oxygen species (ROS) generation, which induces endotheliotoxicity and cardiotoxicity. We hypothesized that Kae could protect vascular endothelium by regulating 14-3-3γ or related pathways against Dox toxicity. HUVECs were established Dox-toxic injury models. Kae's effects were assessed with many physiological, enzymatic, cellular, and molecular biological indexes...

OBJECTIVES: Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism of ischaemic postconditioning...

The aberrant accumulation of iron causes vascular endothelium damage, which is thought to be associated with excess reactive oxygen species (ROS) generation. Quercetin (Que), as a flavonoid, has a certain ability to scavenge free radicals. Therefore, we aimed to explore the protective mechanism of Que on iron overload induced HUVECs injury focused on ROS/ADMA/DDAHⅡ/eNOS/NO pathway. In this study, HUVECs was treated with 50 μM iron dextran and 20 μM Que for 48 h. We found that Que attenuated the damages induced by iron, as evidenced by decreased ROS generation, increased DDAHⅡexpression and activity, reduced ADMA level, increased NO content and p-eNOS/eNOS ratio, and eventually caused a decrease in apoptosis...

BACKGROUND: The metabolic syndrome is a cluster of cardiovascular risk factors and is highly predictive for development of cardiovascular diseases. An association between elevated plasma levels of the endogenous inhibitor of nitric oxide synthases asymmetric dimethylarginine (ADMA) and risk of cardiovascular diseases has been demonstrated in numerous epidemiological studies. ADMA can be catabolized by dimethylarginine dimethylaminohydrolase (DDAH) or metabolized through a much less understood alternative pathway by alanine:glyoxylate aminotransferase 2 (AGXT2) with the formation of α-keto-δ-(N,N-dimethylguanidino)valeric acid (ADGV)...