Binding of GSH conjugates to π-GST: A cross-docking approach

Lannutti, F; Marrone, Alessandro; Re, Nazzareno

doi:10.1016/j.jmgm.2011.09.006

Cited by 9 publications

(8 citation statements)

References 53 publications

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“…GST is a member of the superfamily of multifunctional dimeric proteins involved in the cellular detoxification of cytotoxic and genotoxic compounds and in the prevention of tissue oxidative damages. In addition to their role in catalyzing the conjugation of electrophilic substrates to GSH, these enzymes also carry out a range of other functions in cells, such as the removal of reactive oxygen species and regeneration of S-thiolated proteins (both of which are consequences of oxidative stress), catalysis of conjugations with endogenous ligands, and catalysis of reactions in metabolic pathways not associated with detoxification [45,46]. Finally, the effectiveness of glutathione-based antioxidant defense mechanism is reinforced by the diminished levels of lipid peroxidation in treated cells, as indicated by the reduced concentration of MDA, a secondary product of lipid peroxidation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

et al. 2015

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Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.

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Section: Resultsmentioning

confidence: 99%

Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

et al. 2015

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“…Moreover, the observations that Alpha-, Mu-, and Pi-class GSTs are subject to product inhibition led to investigation of GSH S-conjugates as GST inhibitors (Meyer 1993;Quesada-Soriano et al 2012). A cross-docking approach has been used to investigate the binding of GSH S-conjugates to GSTP (Lannutti et al 2012). Preparation and testing of a panel of GSH analogs as potential isozyme-selective GST inhibitors showed that compound 102 (Figure 9) is a potent inhibitor of hGSTP1-1 (K i ¼ 0.42 lM) and is 58-fold or 438-fold more potent as an inhibitor of hGSTP1-1 than of hGSTA1-1 and hGSTM1a-1a or hGSTM2-2 (Flatgaard et al 1993;Lyttle et al 1994a;Oakley et al 1997).…”

Section: Tissue and Species Distributionmentioning

confidence: 99%

The mercapturic acid pathway

Hanna

Anders

2019

Critical Reviews in Toxicology

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The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (N-acetyl-L-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, c-glutamyltransferases, dipeptidases, and cysteine S-conjugate N-acetyltransferase to yield glutathione S-conjugates, L-cysteinylglycine S-conjugates, L-cysteine S-conjugates, and mercapturic acids; these metabolites constitute a "mercapturomic" profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine S-conjugates. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals. Although mercapturic acid formation and elimination is a detoxication reaction, L-cysteine S-conjugates may undergo bioactivation by cysteine Sconjugate b-lyase. Moreover, some L-cysteine S-conjugates, particularly L-cysteinyl-leukotrienes, exert significant pathophysiological effects. Finally, some enzymes of the mercapturic acid pathway are described as the so-called "moonlighting proteins," catalytic proteins that exert multiple biochemical or biophysical functions apart from catalysis.

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“…Targeted and precise individual therapy is the key step in overcoming MDR [32]. Exploration of MDR-related molecules such as proteins, enzymes, miRNA, lncRNA, circular RNA, cholesterol, folic acid, etc., and development of those molecules to biological targets for reversal of MDR have become a current focus [33][34][35][36][37][38][39]. For example, clinical trials with folic acid and enzymes have been conducted, as shown in Table 5 (No.…”

Section: Discussionmentioning

confidence: 99%

A 10-year bibliometric analysis of osteosarcoma and cure from 2010 to 2019

Tao

Meng

et al. 2021

BMC Cancer

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Background In recent decades, the 5-year survival rate of osteosarcoma remains poor, despite the variety of operations, and exploration of drug therapy has become the key to improvement. This study investigates the contribution of different aspects in osteosarcoma and cure, and predicts research hotspots to benefit future clinical outcomes. Methods The Web of Science and PubMed databases were queried to collect all relevant publications related to osteosarcoma and cure from 2009 to 2019. These data were imported into CiteSpace and the Online Analysis Platform of Literature Metrology for bibliometric analysis. Bi-clustering was performed on Bibliographic Item co-occurrence Matrix Builder (BICOMB) and gCLUTO to identify hotspots. Additionally, completed clinical trials on osteosarcoma with results past phase II were collated. Results A total of 2258 publications were identified in osteosarcoma and cure from 2009 to 2019. China has the largest number of publications (38.49%), followed by the United States (23.03%) with the greatest impact (centrality = 0.44). The centrality of most institutions is < 0.1, and Central South University and Texas MD Anderson Cancer Center possess the highest average citation rates of 3.25 and 2.87. BMC cancer has the highest average citation rate of 3.26 in 772 journals. Four authors (Picci P, Gorlick R, Bielack SS and Bacci G) made the best contributions. We also identified eight hotspots and collected 41 clinical trials related to drug research on osteosarcoma. Conclusions The urgent need exists to strengthen global academic exchanges. Overcoming multidrug resistance in osteosarcoma is the focus of past, present and future investigations. Transformation of the metastasis pattern, microenvironment genetics mechanism, alternative methods of systemic chemotherapy and exploration of traditional Chinese medicine is expected to contribute to a new upsurge of research.

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Binding of GSH conjugates to π-GST: A cross-docking approach

Cited by 9 publications

References 53 publications

Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

The mercapturic acid pathway

A 10-year bibliometric analysis of osteosarcoma and cure from 2010 to 2019

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