728 - Molecular and Functional Defect in ABCG2 Mediated Intestinal Uric Acid Secretion from the Mouse Model of Gout Risk Variant, ABCG2 Q140K

2018 ◽  
Vol 154 (6) ◽  
pp. S-150
Author(s):  
Mirajul H. Kazi ◽  
Owen M. Woodward
Keyword(s):  
Uric Acid ◽  
Mouse Model ◽  
Acid Secretion ◽  
Risk Variant ◽  
Functional Defect ◽  
Uric Acid Secretion

scholarly journals Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity

2013 ◽  
Vol 288 (38) ◽  
pp. 27138-27149 ◽  
Author(s):  
Yu Tsushima ◽  
Hitoshi Nishizawa ◽  
Yoshihiro Tochino ◽  
Hideaki Nakatsuji ◽  
Ryohei Sekimoto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Uric Acid ◽  
Acid Secretion ◽  
Acid Production ◽  
Culture Medium ◽  
Dependent Manner ◽  
Obese Mice ◽  
Subsequent Increase ◽  
Dose Dependent ◽  
Uric Acid Secretion

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity.

scholarly journals High Uric Acid Inhibits Cardiomyocyte Viability Through the ERK/P38 Pathway via Oxidative Stress

2018 ◽  
Vol 45 (3) ◽  
pp. 1156-1164 ◽  
Author(s):  
Zhi Li ◽  
Yang Shen ◽  
Yingqun Chen ◽  
Guokai Zhang ◽  
Jidong Cheng ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Uric Acid ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Ros Production ◽  
Extracellular Signal ◽  
H9c2 Cardiomyocytes ◽  
Pre Treatment ◽  
The Impact ◽  
High Uric Acid

Background/Aims: Clinical studies have shown that hyperuricaemia is strongly associated with cardiovascular disease. However, the molecular mechanisms of high uric acid (HUA) associated with cardiovascular disease remain poorly understood. In this study, we investigated the effect of HUA on cardiomyocytes. Methods: We exposed H9c2 cardiomyocytes to HUA, then cell viability was determined by MTT assay, and reactive oxygen species’ (ROS) production was detected by a fluorescence assay. Western blot analysis was used to examine phosphorylation of extracellular signal-regulated kinase (ERK), p38, phosphatidylinositol 3-kinase (PI3K) and Akt. We monitored the impact of HUA on phospho-ERK and phospho-p38 levels in myocardial tissue from an acute hyperuricaemia mouse model established by potassium oxonate treatment. Results: HUA decreased cardiomyocyte viability and increased ROS production in cardiomyocytes; pre-treatment with N-acetyl-L-cysteine, a ROS scavenger, and PD98059, an ERK inhibitor, reversed HUA-inhibited viability of cardiomyocytes. Further examination of signal transduction pathways revealed HUA-induced ROS involved in activating ERK/P38 and inhibiting PI3K/Akt in cardiomyocytes. Furthermore, the acute hyperuricaemic mouse model showed an increased phospho-ERK/p38 level in myocardial tissues. Conclusion: HUA induced oxidative damage and inhibited the viability of cardiomyocytes by activating ERK/p38 signalling, for a novel potential mechanism of hyperuricaemic-related cardiovascular disease.

scholarly journals Bioactive Compounds from Plant-Based Functional Foods: A Promising Choice for the Prevention and Management of Hyperuricemia

Foods ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 973
Author(s):  
Lin-Lin Jiang ◽  
Xue Gong ◽  
Ming-Yue Ji ◽  
Cong-Cong Wang ◽  
Jian-Hua Wang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Side Effects ◽  
Bioactive Compounds ◽  
Functional Foods ◽  
High Serum ◽  
Pharmacological Effects ◽  
Pharmaceutical Drugs ◽  
Natural Remedies ◽  
Obesity Hypertension ◽  
Uric Acid Secretion

Hyperuricemia is a common metabolic disease that is caused by high serum uric acid levels. It is considered to be closely associated with the development of many chronic diseases, such as obesity, hypertension, hyperlipemia, diabetes, and cardiovascular disorders. While pharmaceutical drugs have been shown to exhibit serious side effects, and bioactive compounds from plant-based functional foods have been demonstrated to be active in the treatment of hyperuricemia with only minimal side effects. Indeed, previous reports have revealed the significant impact of bioactive compounds from plant-based functional foods on hyperuricemia. This review focuses on plant-based functional foods that exhibit a hypouricemic function and discusses the different bioactive compounds and their pharmacological effects. More specifically, the bioactive compounds of plant-based functional foods are divided into six categories, namely flavonoids, phenolic acids, alkaloids, saponins, polysaccharides, and others. In addition, the mechanism by which these bioactive compounds exhibit a hypouricemic effect is summarized into three classes, namely the inhibition of uric acid production, improved renal uric acid elimination, and improved intestinal uric acid secretion. Overall, this current and comprehensive review examines the use of bioactive compounds from plant-based functional foods as natural remedies for the management of hyperuricemia.

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures

2016 ◽  
Vol 277 ◽  
pp. 244-251 ◽  
Author(s):  
Lisa Thyrion ◽  
Robrecht Raedt ◽  
Jeanelle Portelli ◽  
Pieter Van Loo ◽  
Wytse J. Wadman ◽  
...  
Keyword(s):  
Uric Acid ◽  
Mouse Model ◽  
Seizure Activity ◽  
Limbic Seizures ◽  
The Brain

scholarly journals The Role of Hyperuricemia in the Pathogenesis and Progressivity of Chronic Kidney Disease

2021 ◽  
Vol 9 (F) ◽  
pp. 428-435
Author(s):  
Gede Wira Mahadita ◽  
Ketut Suwitra
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Filtration Rate ◽  
Stage Iv ◽  
Review Of The Literature ◽  
The Relationship ◽  
Uric Acid Secretion

In humans, the end product of purine metabolism is uric acid. Over 70% of uric acid is excreted through the kidneys. When renal function is impaired, uric acid secretion is also impaired. This directly correlates the prevalence of hyperuricemia with the severity of chronic kidney disease (CKD). It has been reported that the prevalence of hyperuricemia in patients with Stage I-III CKD is 40–60% and up to 70% in patients with Stage IV-V CKD. Some studies found a link between serum uric acid levels and decreased glomerular filtration rate (GFR), an independent risk factor for CKD development. Because CKD and serum uric acid levels are related, the relationship between the two frequently generates controversy. As such, this review of the literature discusses the role of uric acid in the pathogenesis and progression of CKD.

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