Direct evidence for the covalent modification of glutathione-S-transferase P1-1 by electrophilic prostaglandins: Implications for enzyme inactivation and cell survival

Sánchez‐Gómez, Francisco J.; Gayarre, Javier Machín; Avellano, M. Isabel; Pérez‐Sala, Dolores

doi:10.1016/j.abb.2006.10.032

Cited by 36 publications

(46 citation statements)

References 41 publications

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“…Western blot analysis was performed as described previously (Sá nchez-Gómez et al, 2007). Antibodies and dilutions used were the following: at 1:1000, anti-GSTP1-1 (BD Biosciences, San Jose, CA), anti-c-Jun (Santa Cruz Biotechnology, Santa Cruz, CA), and anti-AU5 (Babco, Berkeley, CA); at 1:500, anti-JNK and anti-p-JNK (Cell Signaling Technology, Danvers, MA).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, treatment with 15d-PGJ 2 elicited various oxidative modifications of GSTP1-1. 15d-PGJ 2 -induced GSTP1-1 modifications were associated with an irreversible inhibition of GSTP1-1 enzymatic activity and with an impairment of its protective effect on cell survival (Sá nchez-Gómez et al, 2007).…”

Section: Introductionmentioning

confidence: 94%

“…1B). Jurkat cells, in which the expression of GSTP1-1 has been characterized previously (Sá nchez-Gómez et al, 2007), were treated with the various agents for 16 h. To avoid disulfide exchange and protein aggregation during sample processing, lysates were obtained in the presence of 50 mM iodoacetamide according to the method of Cumming et al (2004). All agents tested induced GSTP1-1 oligomerization, although with different patterns.…”

Section: D-pgj 2 Induces Gstp1-1 Cross-linking Whereasmentioning

confidence: 99%

“…Thus, according to these results, Cys101 is the only residue essential for 15d-PGJ 2 -induced GSTP1-1 cross-linking. We showed previously that a biotinylated 15d-PGJ 2 analog (15d-PGJ 2 -B) directly bound to endogenous GSTP1-1 in cells (Sá nchez- Gómez et al, 2007). To assess the site of modification of GSTP1-1 in cells, we transfected Jurkat cells with AU5-tagged GSTP1-1 constructs.…”

Section: D-pgj 2 Induces Gstp1-1 Cross-linking Whereasmentioning

confidence: 99%

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Cyclopentenone Prostaglandins with Dienone Structure Promote Cross-Linking of the Chemoresistance-Inducing Enzyme Glutathione Transferase P1-1

Sánchez‐Gómez¹,

Díez-Dacal²,

Pajares³

et al. 2010

Mol Pharmacol

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Glutathione transferase P1-1 (GSTP1-1) plays crucial roles in cancer chemoprevention and chemoresistance and is a key target for anticancer drug development. Oxidative stress or inhibitor-induced GSTP1-1 oligomerization leads to the activation of stress cascades and apoptosis in various tumor cells. Therefore, bivalent glutathione transferase (GST) inhibitors with the potential to interact with GST dimers are been sought as pharmacological and/or therapeutic agents. Here we have characterized GSTP1-1 oligomerization in response to various endogenous and exogenous agents. Ethacrynic acid, a classic GSTP1-1 inhibitor, 4-hydroxy-nonenal, hydrogen peroxide, and diamide all induced reversible GSTP1-1 oligomerization in Jurkat leukemia cells through the formation of disulphide bonds involving Cys47 and/or Cys101, as suggested by reducing and nonreducing SDS-polyacrylamide gel electrophoresis analysis of cysteine to serine mutants. Remarkably, the electrophilic prostanoid 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) induced irreversible GSTP1-1 oligomerization, specifically involving Cys101, a residue present in the human but not in the murine enzyme. 15d-PGJ 2 -induced GSTP1-1 cross-linking required the prostaglandin (PG) dienone structure and was associated with sustained c-Jun NH 2 -terminal kinase activation and induction of apoptosis. It is noteworthy that 15d-PGJ 2 elicited GSTP1-1 cross-linking in vitro, a process that could be mimicked by other dienone cyclopentenone PG, such as ⌬ 12 -PGJ 2 , and by the bifunctional thiol reagent dibromobimane, suggesting that cyclopentenone PG may be directly involved in oligomer formation. Remarkably, ⌬ 12 -PGJ 2 -induced oligomeric species were clearly observed by electron microscopy showing dimensions compatible with GSTP1-1 tetramers. These results provide the first direct visualization of GSTP1-1 oligomeric species. Moreover, they offer novel strategies for the modulation of GSTP1-1 cellular functions, which could be exploited to overcome its role in cancer chemoresistance.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: D-pgj 2 Induces Gstp1-1 Cross-linking Whereasmentioning

confidence: 99%

Section: D-pgj 2 Induces Gstp1-1 Cross-linking Whereasmentioning

confidence: 99%

See 2 more Smart Citations

Cyclopentenone Prostaglandins with Dienone Structure Promote Cross-Linking of the Chemoresistance-Inducing Enzyme Glutathione Transferase P1-1

Sánchez‐Gómez¹,

Díez-Dacal²,

Pajares³

et al. 2010

Mol Pharmacol

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“…Certain proteins are particularly prone to modification by endogenous or exogenous electrophiles. That is the case of GSTP1-1, which is the target for modification by cyclopentenone prostaglandins, ethacrynic acid, and chlorambucil [39][40][41]. Some of these reactive compounds can compete for the same sites on the protein [41].…”

Section: Interactions With Inflammationmentioning

confidence: 99%

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

González-Morena¹,

Montanez²,

Aldini³

et al. 2017

CPD

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Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions. Nevertheless, non-covalent interactions of drugs with receptors in immune cells or with MHC clefts and/or exposed peptides can also play an important role. In recent years, development of proteomic approaches has allowed the identification and characterization of the protein targets for modification by drugs in vivo and in vitro, the nature of peptides exposed on MHC molecules, the changes in protein levels induced by drug treatment, and the concomitant modifications induced by danger signals, thus providing insight into context factors. Nevertheless, given the complexity and multifactorial nature of drug hypersensitivity reactions, understanding the underlying mechanisms also requires the integration of knowledge from genomic, metabolomic and clinical studies.

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Asthma and allergic rhinitis associate with the rs2229542 variant that induces a p.Lys90Glu mutation and compromises AKR1B1 protein levels

et al. 2018

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Asthma and rhinitis are two of the main clinical manifestations of allergy, in which increased reactive oxygen or electrophilic species can play a pathogenic role. Aldose reductase (AKR1B1) is involved in aldehyde detoxification and redox balance. Recent evidence from animal models points to a role of AKR1B1 in asthma and rhinitis, but its involvement in human allergy has not been addressed. Here, the putative association of allergic rhinitis and asthma with AKR1B1 variants has been explored by analysis of single-strand variants on the AKR1B1 gene sequence in 526 healthy subjects and 515 patients with allergic rhinitis, 366 of whom also had asthma. We found that the rs2229542 variant, introducing the p.Lys90Glu mutation, was significantly more frequent in allergic patients than in healthy subjects. Additionally, in cells transfected with expression vectors carrying the wild-type or the p.Lys90Glu variant of AKR1B1, the mutant consistently attained lower protein levels than the wild-type and showed a compromised thermal stability. Taken together, our results show that the rs2229542 variant associates with asthma and rhinitis, and hampers AKR1B1 protein levels and stability. This unveils a connection between the genetic variability of aldose reductase and allergic processes.

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Direct evidence for the covalent modification of glutathione-S-transferase P1-1 by electrophilic prostaglandins: Implications for enzyme inactivation and cell survival

Cited by 36 publications

References 41 publications

Cyclopentenone Prostaglandins with Dienone Structure Promote Cross-Linking of the Chemoresistance-Inducing Enzyme Glutathione Transferase P1-1

Cyclopentenone Prostaglandins with Dienone Structure Promote Cross-Linking of the Chemoresistance-Inducing Enzyme Glutathione Transferase P1-1

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

Asthma and allergic rhinitis associate with the rs2229542 variant that induces a p.Lys90Glu mutation and compromises AKR1B1 protein levels

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