In vitro effect of oxidized and reduced glutathione peptides on angiotensin converting enzyme purified from human plasma

Başı, Zehra; Türkoğlu, Vedat

doi:10.1016/j.jchromb.2018.11.023

Cited by 22 publications

(17 citation statements)

References 44 publications

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“…First, it can be due to the increased renin activity, which is not affected by GSH. Instead, ACE expression and activity are modulated by glutathione; in fact, the oxidized form GSSG shows an activating effect on ACE activity, whereas the reduced GSH provides an inhibitory effect [28]. Finally, the boosted ANGII production can be due to decreased ACE2 expression and activity; this is the case with coronavirus infection, which recognizes ACE2 as its extracellular binding site [29].…”

Section: The Beneficial Effects Of Gsh On the Inflammation Driven By mentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.

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Section: The Beneficial Effects Of Gsh On the Inflammation Driven By mentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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“…The inhibition type of captopril was found as non-competitive from the Lineweaver-Burk chart and the K i value was 0.39 nM (Table 2). In our previous study, the inhibition effect of lisinopril on ACE purified from human plasma was studied and the IC 50 value was found to be 0.781 nM [58]. In many studies, it has been observed that thiol-containing inhibitors such as captopril can exhibit noncompetitive inhibitory effects by forming strong bonds with zinc near the enzyme's active site.…”

Section: Resultsmentioning

confidence: 99%

Purification and characterization of angiotensin-converting enzyme (ACE) from sheep lung

2021

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Angiotensin-converting enzyme (ACE, EC 3.4.15.1) in the renin-angiotensin system regulates blood pressure by catalyzing angiotensin I to the vasoconstrictor angiotensin II. In this study, the ACE was purified and characterized from sheep lung. The kinetic properties of the ACE were designated. The inhibition effect of captopril, a specific ACE inhibitor, was determined. ACE was purified from sheep lung using the affinity chromatography method in one step. NHS-activated Sepharose 4 Fast Flow as column filler and lisinopril as a ligand in this method used. The molecular weight and purity of ACE were designated using the SDS-PAGE method. Optimum temperature and optimum pH were found for purified ACE. K M and V max values from Lineweaver-Burk charts determined. The inhibition type, IC 50 , and K i values of captopril on purified ACE were identified. ACE was 6405-fold purified from sheep lung by affinity chromatography in one step and specific activity was 16871 EU/mg protein. The purity and molecular weight of ACE were found with SDS-PAGE and observed two bands at around 60 kDa and 70 kDa on the gel. Optimum temperature and optimum pH were designated for purified ACE. Optimum temperature and pH were found as 40 °C and pH 7.4, respectively. V max and K M values were calculated to be 35.59 (µmol/ min).mL −1 and 0.18 mM, respectively. IC 50 value of captopril was found as 0.51 nM. The inhibition type of captopril was determined as non-competitive from the Lineweaver-Burk graph and the K i value was 0.39 nM. As a result, it was observed in this study that the ACE enzyme can be successfully purified from sheep lungs in one step. Also, it was determined that captopril, which is a specific ACE inhibitor, has a significant inhibitory effect with a very low IC 50 value of 0.51 nM.

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“…Although it has been previously reported that GSH inhibits ACE activity, the underlying molecular mechanism has not been discussed. 13) Therefore, we first showed that γ-EC inhibited ACE activity and proposed a new model in which the carboxyl group of Glu interacts with the Zn 2+ of ACE via docking simulation.…”

Section: Structural Analysis Of Mechanism Of Conformational Stability Between γ-Ec and Acementioning

confidence: 99%

Inhibitory Activity and Proposed Binding Model of γ-Glutamyl Cysteine, the Precursor of Glutathione, on Angiotensin Converting Enzyme

et al. 2021

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Owing to their various physiological activities, thiol compounds, such as l-cysteine with UV-protection properties and captopril that inhibits the catalytic activity of angiotensin converting enzyme (ACE), are currently used as supplements and pharmaceuticals. Glutathione (GSH) plays an important role in intracellular protective effects and is currently used for the treatment of cataract and detoxification from metal poisoning. In contrast to GSH, the GSH precursor γ-glutamyl cysteine (γ-EC) has been reported to exhibit neuroprotective effects, thus making it an attractive key biological protective molecule. However, its characteristics are largely unknown. Here, we evaluated the ACE inhibitory function of γ-EC and its mechanism by comparing it with that of GSH in vitro. ACE inhibitory analysis showed that the IC 50 of GSH and γ-EC against ACE were 8.3 μM and 3.9 × 10 2 μM, respectively. These data suggested that γ-EC exerted ACE inhibitory activity, but it was weaker than that of GSH. Docking simulation showed that the ACE inhibitory activity of both compounds was due to the interaction of their carboxyl groups of Glu with Zn 2+ in the active center of ACE. Moreover, GSH could fit more compactly in the pocket of ACE, forming more hydrogen bonds with the enzyme than γ-EC. By analyzing its kinetics and in vivo efficacy, we hope that γ-EC could be used as a promising compound for lowering blood pressure in applications with moderate activity, such as functional foods.Key words thiol, γ-glutamyl cysteine, angiotensin converting enzyme Fig. 1. The Structure of GSH and Its Precursor γ-EC Structural formulas of (a) GSH and (b) γ-EC. GSH is a tripeptide consisting of Glu, Cys, and Gly. γ-EC is a dipeptide consisting of Glu and Cys. Both have unusual γ-peptide bonds between Glu and Cys.

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In vitro effect of oxidized and reduced glutathione peptides on angiotensin converting enzyme purified from human plasma

Cited by 22 publications

References 44 publications

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

Purification and characterization of angiotensin-converting enzyme (ACE) from sheep lung

Inhibitory Activity and Proposed Binding Model of γ-Glutamyl Cysteine, the Precursor of Glutathione, on Angiotensin Converting Enzyme

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