Kinetic features of carbonyl reductase 1 acting on glutathionylated aldehydes

Moschini, Roberta; Rotondo, Rossella; Renzone, Giovanni; Balestri, Francesco; Cappiello, Mario; Scaloni, Andrea; Mura, Umberto; Corso, Antonella Del

doi:10.1016/j.cbi.2017.03.003

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…This effect accounted for approximately 40% of inhibition. The failure of sorbinil to completely inhibit the GSHNE reducing activities may be due to the fact that also CBR1, which is insensitive to Sorbinil [52], may catalyse the NADPH-dependent reduction of GSHNE [30].…”

Section: Hne and Gshne Detoxification Pathways In Adf Cells Crude Extractsmentioning

confidence: 99%

Pathways of 4-Hydroxy-2-Nonenal Detoxification in a Human Astrocytoma Cell Line

Peroni¹,

Scali

Balestri

et al. 2020

Antioxidants

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One of the consequences of the increased level of oxidative stress that often characterizes the cancer cell environment is the abnormal generation of lipid peroxidation products, above all 4-hydroxynonenal. The contribution of this aldehyde to the pathogenesis of several diseases is well known. In this study, we characterized the ADF astrocytoma cell line both in terms of its pattern of enzymatic activities devoted to 4-hydroxynonenal removal and its resistance to oxidative stress induced by exposure to hydrogen peroxide. A comparison with lens cell lines, which, due to the ocular function, are normally exposed to oxidative conditions is reported. Our results show that, overall, ADF cells counteract oxidative stress conditions better than normal cells, thus confirming the redox adaptation demonstrated for several cancer cells. In addition, the markedly high level of NADP+-dependent dehydrogenase activity acting on the glutahionyl-hydroxynonanal adduct detected in ADF cells may promote, at the same time, the detoxification and recovery of cell-reducing power in these cells.

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Section: Hne and Gshne Detoxification Pathways In Adf Cells Crude Extractsmentioning

confidence: 99%

Pathways of 4-Hydroxy-2-Nonenal Detoxification in a Human Astrocytoma Cell Line

Peroni¹,

Scali

Balestri

et al. 2020

Antioxidants

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“…A full description of the model (and ODEs) together with the description and values (when available) of all kinetic constants ,− is given in the Supporting Information S1 (Tables S1 and S2); Supporting Material S2 contains the metabolic model in SBML format.…”

Section: Methodsmentioning

confidence: 99%

Simulation and Reconstruction of Metabolite–Metabolite Association Networks Using a Metabolic Dynamic Model and Correlation Based Algorithms

2019

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Biological networks play a paramount role in our understanding of complex biological phenomena and metabolite-metabolite association networks are now commonly used in metabolomics applications. In this study we evaluate the performance of several network inference algorithms (PCLRC, MRNET, GENIE3, TIGRESS and modifications of the MR-NET algorithm, together with standard Pearson's and Spearman's correlation) using as a test case data generated using a dynamic metabolic model describing the metabolism of arachidonic acid (consisting of 83 metabolites and 131 reactions) and simulation individual metabolic profiles of 550 subjects. The quality of the reconstructed metabolite-metabolite association networks was assessed against the original metabolic network taking into account different degrees of association among the metabolites and different sample size and

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“…This aldehydic compound can be metabolized either through its conjugation with glutathione via Michael addition, which occurs both spontaneously and upon the action of different glutathione S-transferases [ 29 , 30 ], to generate 3-glutathionyl-4-hydroxynonal (GSHNE), or upon red/ox transformations (occurring both on HNE and on GSHNE) catalyzed by oxidoreductases, whose abundance and specificity are strictly tissue-dependent [ 31 , 32 , 33 , 34 , 35 ]. In particular, concerning GSHNE, besides AKR1B1, which has been demonstrated to be able to participate not only to HNE but also in the adduct reduction [ 13 ], carbonyl reductase 1 (CBR1) has been more recently indicated as being effective in catalyzing GSHNE transformation [ 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Response of a Human Lens Epithelial Cell Line to Hyperglycemic and Oxidative Stress: The Role of Aldose Reductase

et al. 2023

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A common feature of different types of diabetes is the high blood glucose levels, which are known to induce a series of metabolic alterations, leading to damaging events in different tissues. Among these alterations, both increased polyol pathway flux and oxidative stress are considered to play relevant roles in the response of different cells. In this work, the effect on a human lens epithelial cell line of stress conditions, consisting of exposure to either high glucose levels or to the lipid peroxidation product 4-hydroxy-2-nonenal, is reported. The occurrence of osmotic imbalance, alterations of glutathione levels, and expression of inflammatory markers was monitored. A common feature of the two stress conditions was the expression of COX-2, which, only in the case of hyperglycemic stress, occurred through NF-κB activation. In our cell model, aldose reductase activity, which is confirmed as the only activity responsible for the osmotic imbalance occurring in hyperglycemic conditions, seemed to have no role in controlling the onset of the inflammatory phenomena. However, it played a relevant role in cellular detoxification against lipid peroxidation products. These results, in confirming the multifactorial nature of the inflammatory phenomena, highlight the dual role of aldose reductase as having both damaging but also protecting activity, depending on stress conditions.

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Kinetic features of carbonyl reductase 1 acting on glutathionylated aldehydes

Cited by 7 publications

References 40 publications

Pathways of 4-Hydroxy-2-Nonenal Detoxification in a Human Astrocytoma Cell Line

Pathways of 4-Hydroxy-2-Nonenal Detoxification in a Human Astrocytoma Cell Line

Simulation and Reconstruction of Metabolite–Metabolite Association Networks Using a Metabolic Dynamic Model and Correlation Based Algorithms

Response of a Human Lens Epithelial Cell Line to Hyperglycemic and Oxidative Stress: The Role of Aldose Reductase

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