Aminoacylase 1-catalysed deacetylation of bioactives epoxides mycotoxin-derived mercapturates; 3,4-epoxyprecocenes as models of cytotoxic epoxides

Stocker, Pierre; Brunel, Jean Michel; Rezende, Leandro de; Amaral, Antônia Tavares do; Morelli, Xavier; Roche, Phillipe; Vidal, Nicolás; Giardina, Thierry; Perrier, Josette

doi:10.1016/j.biochi.2012.01.006

Cited by 7 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human and porcine Acy1 also catalyze the hydrolysis of a mercapturic acid formed from 3,4-epoxyprecocene II epoxide as well as several other synthetic mercapturic acids. (Stocker et al 2012).…”

Section: Substratesmentioning

confidence: 99%

The mercapturic acid pathway

Hanna

Anders

2019

Critical Reviews in Toxicology

View full text Add to dashboard Cite

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.

show abstract

Section: Substratesmentioning

confidence: 99%

The mercapturic acid pathway

Hanna

Anders

2019

Critical Reviews in Toxicology

View full text Add to dashboard Cite

show abstract

“…Additionally, to analyse the similarity between the 3D structures of each complex, the following properties were calculated: hydrogen bonding sites (HB) 42 and lipophilic potential (LP). 43,44 Each property was colour coded and mapped onto the corresponding surface in order to investigate, by visual inspection, 45 the importance of each property to the peculiar reactivity exhibited by complex 1 in its preferential albumin metal binding site.…”

Section: Molecular Properties Analysismentioning

confidence: 99%

Peculiar reactivity of a di-imine copper(ii) complex regarding its binding to albumin protein

et al. 2013

Self Cite

View full text Add to dashboard Cite

A set of four di-imine copper(II) complexes containing pyridine, pyrazine and/or imidazole moieties, [Cu(apyhist)H2O](2+) 1 (apyhist = 2-(1H-imidazol-4-yl)-N-(1-(pyridin-2-yl)ethylidene)ethanamine), [Cu(apzhist)OH](+) 2 (apzhist = 2-(1H-imidazol-4-yl)-N-(1-(pyrazin-2-yl)ethylidene)ethanamine), [Cu(apyepy)OH](+) 3 (apyepy = 2-(pyridin-2-yl)-N-(1-(pyridin-2-yl)ethylidene)ethanamine), and [Cu(apzepy)H2O](2+) 4 (apzepy = N-(1-(pyrazin-2-yl)ethylidene)-2-(pyridin-2-yl)ethanamine), were investigated regarding their capability of interacting with serum albumin (human, HSA and bovine, BSA), by using spectroscopic techniques, CD, UV/Vis and EPR. Like other similar di-imine copper(II) complexes, most of them showed an expected preferential insertion of the metal ion at the primary N-terminal site of the protein, very selective for copper and characterized by a CD band at 560 nm. Further insertion of the copper ion at a secondary site is expected when using an excess of the metal. However, one of these studied complexes, [Cu(apyhist)H2O](2+) 1, exhibited anomalous behaviour interacting only at this secondary metal binding site of albumin, characterized by a CD band at 370 nm, and attributed to the coordination of copper at the Cys34 pocket. Analogous experiments with HSA previously treated with N-ethyl-maleimide (NEM), that oxidizes the protein Cys34 residue and obstructs the metal coordination, verified these results. Additional data obtained by EPR spectroscopy complemented those results. DFT calculations, considering some structural and electronic characteristics of such series of di-imine ligands and of the corresponding copper complexes, suggested molecular recognition of the apyhist ligand at the protein cavity as a feasible explanation for this unexpected and peculiar behaviour of complex 1.

show abstract

“…Its deregulation has been associated with autism and convulsions (24,25). ACY1 has also been reported to play a role in the deacetylation of aflatoxin epoxy derivatives and thereby influence cell detoxification function (26). Moreover, studies have found ACY1 to be strongly implicated in carcinogenesis, with different roles in different types of cancers.…”

Section: Discussionmentioning

confidence: 99%

ACY1 regulating PTEN/PI3K/AKT signaling in the promotion of non-small cell lung cancer progression

Chen¹,

Wang²,

Xiao³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis and is the most common cause of cancer-related deaths worldwide. Aminoacylase 1 (ACY1) plays a promoting role in some cancers, but its role in NSCLC is still unclear. Methods: Immunohistochemistry, Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting assays were used to determine ACY1 expression patterns in NSCLC tissues and cell lines. The clinical significance of ACY1 in NSCLC was evaluated by χ 2 test and Kaplan-Meier analysis. MTT, flow cytometry, wound healing, and Transwell assays were performed to assess cell growth, apoptosis, migration, invasion, and tumorigenesis under different treatments. Male athymic BALB/C nude mice were used for xenotransplantation experiments.Results: The results showed that ACY1 expression was elevated in NSCLC tissue samples and cells, and high ACY1 expression predicted an advanced clinical process and shorter overall survival in patients with NSCLC. Overexpression of ACY1 significantly increased cell growth, migration, invasion, and tumorigenesis, and reduced cell apoptosis, indicating that ACY1 functions as an oncogene in NSCLC.Moreover, ACY1 decreased phosphatase and tensin homolog (PTEN) expression, increased its ubiquitination, and activated PI3K/AKT signaling. Overexpression of PTEN diminished the effects of ACY1 upregulation on cell tumorigenesis promotion.Conclusions: This study reveals that ACY1 may promote the progression of NSCLC via activating PI3K/AKT signaling in a PTEN-dependent manner. Our study may provide a better understanding of the pathogenesis and development of NSCLC.

show abstract

Aminoacylase 1-catalysed deacetylation of bioactives epoxides mycotoxin-derived mercapturates; 3,4-epoxyprecocenes as models of cytotoxic epoxides

Cited by 7 publications

References 29 publications

The mercapturic acid pathway

The mercapturic acid pathway

Peculiar reactivity of a di-imine copper(ii) complex regarding its binding to albumin protein

ACY1 regulating PTEN/PI3K/AKT signaling in the promotion of non-small cell lung cancer progression

Contact Info

Product

Resources

About