6PGD Enzyme Activities Research Articles

Histone deacetylase 7 activates 6-phosphogluconate dehydrogenase via an enzyme-independent mechanism that involves the N-terminal protein-protein interaction domain.

Histone deacetylase 7 (HDAC7) is a member of the class IIa family of classical HDACs with important roles in cell development, differentiation, and activation, including in macrophages and other innate immune cells. HDAC7 and other class IIa HDACs act as transcriptional repressors in the nucleus but, in some cell types, they can also act in the cytoplasm to modify non-nuclear proteins and/or scaffold signalling complexes. In macrophages, HDAC7 is a cytoplasmic protein with both pro- and anti-inflammatory functions, with the latter activity involving activation of the pentose phosphate pathway (PPP) enzyme 6-phosphogluconate dehydrogenase (6PGD) and the generation of anti-inflammatory metabolite ribulose-5-phosphate. Here, we used ectopic expression systems and biochemical approaches to investigate the mechanism by which HDAC7 promotes 6PGD enzyme activity. We reveal that HDAC7 enzyme activity is not required for its activation of 6PGD and that the N-terminal protein-protein interaction domain of HDAC7 is sufficient to initiate this response. Mechanistically, the N-terminus of HDAC7 increases the affinity of 6PGD for NADP+, promotes the generation of a shorter form of 6PGD, and enhances the formation of higher order protein complexes, implicating its scaffolding function in engagement of the PPP. This contrasts with the pro-inflammatory function of HDAC7 in macrophages, in which it promotes deacetylation of the glycolytic enzyme pyruvate kinase M2 for inflammatory cytokine production.

The Effects of Sodium Tetraborate against Lead Toxicity in Rats: The Behavior of Some Metabolic Enzymes.

This study was planned to research the in vivo effects of lead (Pb) ions and sodium tetraborate (Na2B4O7) on G6PD and 6PGD, which are some of the enzymes of the pentose phosphate pathway, which carries vital importance for metabolism, and GR and GST, which are glutathione metabolism enzymes, and the in vitro effects of the same agents on the 6PGD enzyme. According to the in vivo analysis results, in comparison to the control group, the rat liver G6PD (p < 0.05), and 6PGD (p < 0.01) enzyme activities in the Na2B4O7 group were significantly lower. In addition, GR and GST enzyme activities were insignificantly lower in the Na2B4O7 group compared to the control group (p > 0.05). The Pb group had lower G6PD and 6PGD enzyme activity levels and higher GR and GST enzyme activity levels compared to the control group, while these changes did not reach statistical significance (p > 0.05). In the in vitro analyses of the effects of Pb ions on the 6PGD enzyme that was purified out of rat liver with the 2',5'-ADP-Sepharose 4B affinity chromatography method, it was determined that Pb ions (200-1200 μM) increased the rat liver 6PGD enzyme activity levels by 33%. On the other hand Na2B4O7 was not significantly effective on 6PGD activity. These results will also contribute to future studies in understanding the physiopathology of the states triggered by Pb ions and sodium tetraborate (Na2B4O7).

Screening of in vitro and in silico effect of Fluorophenylthiourea compounds on glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase enzymes.

Inhibition studies of enzymes in the pentose phosphate pathway (PPP) have recently emerged as a promising technique for pharmacological intervention in several illnesses. Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) are the most important enzymes of the PPP. For this purpose, in the current study, we examined the effect of some fluorophenylthiourea on G6PD and 6PGD enzyme activity. These compounds exhibited moderate inhibitory activity against G6PD and 6PGD with KI values ranging from 21.60 ± 8.42 to 39.70 ± 11.26 μM, and 15.82 ± 1.54 to 29.97 ± 5.72 μM, respectively. 2,6-difluorophenylthiourea displayed the most potent inhibitory effect for G6PD, and 2-fluorophenylthiourea demonstrated the most substantial inhibitory effect for 6PGD. Furthermore, the molecular docking analyses of the fluorophenylthioureas, competitive inhibitors, were performed to understand the binding interactions at the enzymes' binding site.

Alterations in Enzyme Activity of Carbonic Anhydrase, 6-phosphogluconate Dehydrogenase and Thioredoxin Reductase in Rats Exposed to Doxorubicin and Morin

Objective: Carbonic anhydrase (CA), 6-phosphogluconate dehydrogenase (6PGD) and thioredoxin reductase (TrxR) enzymes are the essential biological molecules needed for metabolic processes in all living cells. This study was designed to investigate the activities of CA, 6PGD and TrxR enzymes in the brain, kidney, liver, heart and testis tissues of the rats exposed to Dox and morin. Methods: Male Wistar albino rats were randomly divided into three groups as control, morin and DOX, each of them containing 7 rats. At the end of the experimental procedure, CA, 6PGD and TrxR enzyme activities in tissues of rats were determined spectrophotometrically. Results: In our study, we observed that DOX activated CA enzyme in liver and kidney tissues while inhibiting CA enzyme in the other tissues, activated 6PGD enzyme in the kidney, liver and heart tissues, and inhibited the TrxR enzyme in all the tissues. In addition, morin activated CA enzyme in the liver tissue while inhibiting CA enzyme in the brain, heart and testis tissues. Morin activated 6PGD enzyme activity while it inhibited TrxR enzyme in all the tissues. Conclusion: The findings showed that doxorubicin and morin had similar properties in the tissues as to their effect on enzyme activities.

&lt;p&gt;Discovery of Ebselen as an Inhibitor of 6PGD for Suppressing Tumor Growth&lt;/p&gt;

IntroductionThe 6-phosphogluconate dehydrogenase (6PGD) was upregulated in many solid cancers and plays an important role in tumorigenesis. In the present study, we want to discover an old drug as an inhibitor of 6PGD for suppressing tumor growth.MethodsWe determined the expression of 6PGD in cancer tissues using Gene Expression Omnibus (GEO) profiles and explored the importance of 6PGD expression in cancer progression by using Kaplan–Meier Plotter. We identified Ebselen as a 6PGD inhibitor by using 6PGD in vitro enzyme activity assay. Cell viability, cell proliferation, tumor growth and cell metabolism assay were used to explore the role of 6PGD and its inhibitor in cancer cells.ResultsWe found that the expression of 6PGD was upregulated in different cancer tissues and it can promote tumorigenesis. Here, we analyzed our 6PGD inhibitor screening data again and found an old drug Ebselen, which blocks cancer cell proliferation and tumor growth by inhibiting 6PGD enzyme activity, while knocking down 6PGD would partially abolish the inhibition of Ebselen on cell proliferation and cell metabolism.ConclusionOur results suggested that the conventional drug Ebselen could serve as a novel inhibitor of 6PGD for suppressing cancer growth by inhibiting 6PGD enzyme activity.

The effect of astaxanthin and cadmium on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzymes activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro.

In this study, the effects of astaxanthin (AST) that belongs to carotenoid family and cadmium (Cd), which is an important heavy metal, on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzyme activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro were studied. In in vitro studies, 6PGD enzyme was purified from rat erythrocytes with 2',5'-ADP Sepharose4B affinity chromatography. Results showed inhibition of enzyme by Cd at IC50 ; 346.5μM value and increase of 6PGD enzyme activity by AST. In vivo studies showed an increase in G6PD, 6PGD, and GR enzyme activities (P˃0.05) and no chance in TrxR enzyme activity by AST. Cd ion inhibited G6PD, 6PGD, and GR enzyme activities (P˂0.05) and also decreased TrxR enzyme activity (P˃0.05). AST+Cd group G6PD enzyme activity was statistically low compared with control group (P˂0.05). 6PGD and TrxR enzyme activities decreased without statistical significance (P˃0.05); however, GR enzyme activity increased statistically significantly (P˂0.05).

Effect of astaxanthin and aluminum chloride on erythrocyte G6PD and 6PGD enzyme activities in vivo and on erythrocyte G6PD in vitro in rats.

In this study, we investigated the effect of astaxanthin (Ast) and aluminum (Al) on the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes activities in vivo and on G6PD enzyme in vitro in rats. For in vitro studies, G6PD enzyme was purified from rat erythrocyte by using 2',5'-ADP-Sepharose 4B affinity gel. The effects of Ast and Al3+ ion were investigated on the purified enzyme. It was determined that Ast increased the enzyme activity, whereas Al3+ inhibited the enzyme activity noncompetitively (IC50 values; 0.679mM, Ki values 1.32mM). For in vivo studies, the rats were divided into the groups: control (Cont.), Al, Ast, and Al+Ast. The last three groups were compared with the control group. In Al group, a significant degree of inhibition was observed in the activity of G6PD and 6PGD enzymes when compared with the control group (P<0.05), whereas there was an increase in the activities of G6PD and 6PGD enzymes in Ast and Al+Ast groups (P<0.05).

Examination of changes in enzyme activities of erythrocyte glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in rats given Naringenin and Lead acetate.

In our study, controlled experimental groups were performed by giving substances Lead acetate, Naringenin and Naringenin + Lead acetate to rats in vivo conditions Changes in the glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzyme activities in erythrocytes of rats in these groups were compared to the Control group. An inhibition significant degree for G6PD enzyme activity was observed in all groups when compared to the Control group (p < 0.001). While inhibition significant degree for 6PGD enzyme activity was observed in Lead acetate groups (p < 0.001), no significant effect was observed in the Naringenin and Naringenin + Lead acetate groups (p > 0.05). In addition, lead levels in the groups of rats were determined using an inductively coupled plasma mass spectrometer (ICP-MS) device. As a result of measurements by the ICP-MS device, lead levels were found as an average of 42.9 ± 2.51, 36.71 ± 1.13, 172.16 ± 9.63, and 95.07 ± 5.87 ppm in the Control, Naringenin, Lead acetate and Naringenin + Lead acetate groups, respectively. Our results were shown that Naringenin has protective effects on the Lead acetate induced oxidative stress erythrocytes in rat.

Kinetic Behaviour of Glucose 6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase in Different Tissues of Rainbow Trout (Oncorhynchus mykiss) Exposed to Non-Lethal Concentrations of Cadmium

The effects of cadmium (Cd) on the enzymatic activities of glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were investigated in the gill, liver and kidney tissues of rainbow trout (Oncorhynchus mykiss). Three test groups of fish were subjected to increasing concentrations (1, 3 and 5 mg/l) of cadmium (Cd) in vivo, respectively. The G6PD and 6PGD activities in the gill, liver, and kidney tissues of each group of fish were measured on days 1, 3, 5 and 7. G6PD and 6PGD enzyme activities, measured in gill, liver and kidney homogenates, were stimulated by various concentrations (1, 3, and 5 mg/l) of cadmium. Although the dose-response pattern of G6PD enzyme activities in liver and kidney tissue was very similar, that in gill was different from both other tissues. The enzyme activity of G6PD enzyme was significantly stimulated after three days (Day 3) in liver and kidney tissues at a dose of 1 mg/l Cd (p &lt; 0.05), whereas it was stimulated on the first day of experiment (Day 1) in gill, liver and kidney tissues at doses of 3 and 5 mg/l Cd (p &lt; 0.05). However, the activity of 6PGD was stimulated after three days (Day 3) in the liver at a dose of 1 mg/l Cd (p &lt; 0.05) and on the first day in gill, liver and kidney tissues at doses of 3 and 5 mg/l Cd (p &lt; 0.05). The stimulation effect of the 5 mg/l dose of Cd on G6PD and 6PGD enzyme activities was significantly diminished after seven days (Day 7) in all tissues (p &lt; 0.05). In contrast to the dose-response pattern at the dose of 5 mg/l Cd, G6PD and 6PGD enzyme activities were stimulated significantly (p &lt; 0.05) in liver and kidney tissues at the doses of 3 and 1 mg/l Cd. The stimulation effect of cadmium on the three tissues studied was also calculated; for both of the enzymes (G6PD and 6PGD), the enzyme activity levels were stimulated by approximately 60% and 38% in gills, 68% and 44% in liver, and 67% and 41% in kidneys, respectively, over the base-line enzyme activity of the control groups during the sevenday experimental period. These findings indicate that tissue G6PD and 6PGD enzymes function to protect against cadmium toxicity.

Effects of nicotine and vitamin E on 6-phosphogluconate dehydrogenase activity in some rat tissues in vivo and in vitro

The aim of this study was to investigate whether nicotine affects 6-phosphogluconate dehydrogenase (6PGD) enzyme activity in some rat tissues, and to see the modulatory effects of vitamin E on this effect in vivo. In addition, the effects of nicotine and vitamin E on 6PGD activity were also tested in vitro. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine + vitamin E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. The results of in vivo study showed that nicotine activated the muscle, lungs, and testicular 6PGD enzyme activity but had no effect on heart and liver 6PGD activity. Also, nicotine + vitamin E activated the muscle, testicle, and liver 6PGD enzyme activity, while this combination had no effect on heart, and lungs in vivo. When nicotine is administered with vitamin E the increase in 6PGD enzyme activity in muscle and testicles were lower. On the other hand the increase in 6PGD enzyme activity was eliminated by vitamin E in lungs, while 6PGD enzyme activity was increased by vitamin E, which was not affected by nicotine only. In vitro results correlated well with in vivo experimental results. Our results suggest that vitamin E may favourably increase 6PGD enzyme activity in liver in nicotine treated rats, while it has negligible effects on this enzyme activity in other tissues.