Aldose reductase mediates endothelial cell dysfunction induced by high uric acid concentrations

Huang, Zhiyong; Hong, Quan; Zhang, Xueguang; Xiao, Wu; Wang, Liyuan; Cui, Shaoyuan; Feng, Zhe; Lv, Yang; Cai, Guangyan; Chen, Xiangmei; Wu, Di

doi:10.1186/s12964-016-0158-6

Cited by 52 publications

(51 citation statements)

References 77 publications

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“…UA has been reported to stimulate aldose reductase and fructokinase expression [21,22]. Overactivation of such enzymes initiates a damaging circle as endogenous fructose produced by the polyol pathway feeds fructokinase, depleting intracellular ATP and activating purine degradation pathway that leads to more UA synthesis [7].…”

Section: Discussionmentioning

confidence: 99%

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

et al. 2018

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Background: Heat stress and rhabdomyolysis are major risk factors for the occurrence of repeated acute kidney injury in workers exposed to heat and strenuous work. These episodes, in turn, may progress to chronic kidney disease. Objective: The purpose of this study was to test the effect of allopurinol (AP) and sodium bicarbonate on the kidney injury induced by recurrent heat stress dehydration with concomitant repeated episodes of rhabdomyolysis. Methods: The model consisted of heat stress exposure (1 h, 37°C) plus rhabdomyolysis (R) induced by repetitive IM injections of glycerol (7.5 mL/kg BW days) in the rat. In addition, to replicate the human situation, uricase was inhibited (oxonic acid [OA] 750 mg/K/d) to increase uric acid (UA) levels. Additional groups were treated either with AP 150 mg/L, n = 10, bicarbonate (BC; 160 mM, n = 10), or both (AP + BC, n = 10) in drinking water. We also included 2 control groups consisting of normal controls (N-Ref, n = 5) and uricase-inhibited rats (OA, n = 5) that were not exposed to heat or muscle injury. Groups were studied for 35 days. Results: Uricase-inhibited rats exposed to heat and rhabdomyolysis developed pathway and increased intrarenal oxidative stress and inflammasome activation. Kidney injury could be largely prevented by AP, and also BC, although the treatments were not synergistic. Conclusion: Increased levels of UA may play an important role in the renal alterations induced by heat stress and continuous episodes of rhabdomyolysis. Therefore, treatments aimed to reduce hyperuricemia may help to decrease the renal burden in these conditions. Clinical trials are suggested to test whether this is also true in humans.

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Section: Discussionmentioning

confidence: 99%

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

et al. 2018

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“…For example, uric acid may feedback to increase endogenous fructose production by stimulating AR (149, 150) and may also stimulate fructose metabolism by increasing expression and activity of fructokinase (33). In contrast, high concentrations of uric acid can block xanthine oxidase (151, 152).…”

Section: Modulating Factorsmentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

722

490

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Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

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“…We believed that the concentration of uric acid (300 μM) or the treatment-time (2 hours) were not enough to decrease, at least, the fluorescence intensity of 7-CBA. Uric acid (in the concentration higher than 300 μM and in treatment-time higher than 6 hours) decreased expression and activity of eNOS, reduced NO bioavailability, enhanced ROS generation and induced the apoptosis in HUVECs [33];[34];[35]; [36]. Park et al .…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

Potje

Chen

Oliveira

et al. 2017

Free Radical Biology and Medicine

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[Ru(terpy)(bdq)NO]3+ (TERPY) is a nitric oxide (NO) donor that promotes relaxation of the mesenteric artery and aorta in rats. We sought to investigate whether it acts as both an NO donor and endothelial NO synthase (eNOS) activator, as shown previously for nitroglycerin. Human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 cells transfected with empty vector (HEK) or eNOS cDNA (HEK-eNOS) were treated with TERPY (1 μM) for different lengths of time. eNOS expression, dimerization, and Ser1177 phosphorylation, caveolin-1 (Cav-1) oligomerization, Cav-1 Tyr14 phosphorylation were evaluated by Western blotting. Studies also assessed the production of reactive oxygen/nitrogen species (ROS/RNS) in HUVECs and HEK-eNOS cells. In HEK cells devoid of eNOS, TERPY released NO without additional stimulus indicating that is an NO donor. Moreover, in HEK-eNOS cells, TERPY-induced NO production that was blocked by L-NAME. In addition, TERPY increased ROS and ONOO– production which were blocked by more than 80% by BH4 (essential eNOS co-factor) and eNOS siRNA. These results suggest that TERPY-induced ROS and ONOO− production were originated from eNOS. HUVECs stimulated with TERPY showed increased eNOS Ser1177 and Cav-1 Tyr14 phosphorylation, and decreased eNOS dimerization, Cav-1 oligomerization, and Cav-1/eNOS interaction after 20 min. It suggests that TERPY induces eNOS hyperactivation and uncoupling by disrupting Cav-1/eNOS interaction and depleting BH4. Endothelium-dependent vasodilation in response to NO donor TERPY is associated with eNOS activation and uncoupling, and thereby appears to be mediated, at least in part, via eNOS-dependent ROS/RNS production.

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Aldose reductase mediates endothelial cell dysfunction induced by high uric acid concentrations

Cited by 52 publications

References 77 publications

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

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