English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

: Elevated plasma levels of uric acid ( UA ) are considered an independent risk factor for hypertension, diabetes, cardiovascular disease, endothelial and vascular damage, obesity, and metabolic syndrome. Even physiological concentrations of soluble  UA  have been proved to induce gene expression of macrophage-secreted inflammatory cytokines and stimulate production of reactive oxygen species in mature adipocytes.  UA  is also described as a powerful endogenous plasma antioxidant, which reveals a paradox of duality for this parameter.Aim : The aim of this study was to investigate the effect of  UA  on expression of antioxidant defense related enzymes in cultured J744A.1 macrophage cell line.Materials and methods : Mouse macrophage J744A.1 cells were treated with uric acid at increasing concentrations of 200 to 800 μM. Changes in expression levels of genes related to the metabolism of glutathione – glutamate-cysteine ligase, catalytic subunit ( GCLc ), glutathione peroxidase 1 ( GPx1 ), glutathione reductase ( GR ) and glutathione synthetase ( GS ) were analyzed. Gene expression levels were calculated using the 2 -ΔΔCt  method.Results : When  UA  is applied in concentrations of 200 µM and 400 µM, cell viability did not change significantly. Higher, pathophysiological concentrations of 600 μM, 800 μM  UA , and 1000 μM of  UA  caused significant decrease in cell viability to 95.81% ( p &lt;0.01), 76.22% ( p &lt;0.001), and 18.01% ( p &lt;0.001), respectively.  UA  treatment in concentrations of 200 μM, 400 μM, 500 μM, and 800 μM induced significant transcription levels of glutathione reductase – 8.14 ( p &lt;0.05), 7.15 ( p &lt;0.01), 22.07 ( p &lt;0.001), and 27.77 ( p &lt;0.01), respectively, and of glutathione synthetase – 13.71 ( p &lt;0.01), 13.05 ( p &lt;0.05), 18 ( p &lt;0.01), and 48.60 ( p &lt;0.01) folds, respectively.  GCLc  and  GPx1  genes were transcriptionally activated by higher (500 μM and 800 μM) concentrations of  UA . For these  UA  concentrations the measured levels of mRNA were 7.51 ( p &lt;0.05) and 12 fold ( p &lt;0.05) higher than the non-treated control for  GCLc  and 1.90 ( p &lt;0.05) and 1.93 ( p &lt;0.01) for  GPx1 . Significant difference in the  GCLc  expression was found between the 200 μM and 500 μM ( p &lt;0.05) and 800 μM ( p &lt;0.01) treated cells. mRNA levels were significantly different between 400 μM and 800 μM ( p &lt;0.05) for both  GCLc  and  GR  genes. Very strong correlation was found between  GCLc  and  GR  (0.974,  p =0.005) and  GS  (0.935,  p =0.020) expression and between  GS  and  GR  (0.886,  p =0.045) expression levels.Conclusions : It appears that 500 μM and pathophysiological concentrations (800 μM) of  UA  induce antioxidant cell response in J744A.1 macrophages proved by the indicative elevation  GCL ,  GPx1 ,  GR , and  GS  transcription.  GR  and  GS  can be stimulated even by lower concentrations (200 μM and 400 μM) indicating that glutathione metabolism in macrophages is tightly regulated in order to keep adequate  GSH  levels.

folia medica

Uric acid effects on glutathione metabolism estimated by induction of glutamate-cysteine ligase, glutathione reductase and glutathione synthetase in mouse J744A.1 macrophage cell line