Role of copper and ceruloplasmin in oxidative mutagenesis induced by the glutathione-γ-glutamyl transpeptidase system and by other thiols

Stark, Avishay‐Abraham; Glass, G A

doi:10.1002/(sici)1098-2280(1997)29:1<63::aid-em9>3.0.co;2-e

Cited by 20 publications

(2 citation statements)

References 32 publications

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“…Conversely, γGT has been demonstrated to have pro-oxidant effects. Combined with metal ions (iron or copper), γGT can induce lipid peroxidation (, ; Stark and Glass, 1997). γGT has been linked to reactive oxygen species generation in cells (Drozdz et al, 1998; Del Bello et al, 1999; Paolicchi et al, 2002).…”

Section: Glutathione S-derivatives Activated By γGt and Peptidasesmentioning

confidence: 99%

Glutathione S-conjugates as prodrugs to target drug-resistant tumors

Ramsay

Dilda

2014

Front. Pharmacol.

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Living organisms are continuously exposed to xenobiotics. The major phase of enzymatic detoxification in many species is the conjugation of activated xenobiotics to reduced glutathione (GSH) catalyzed by the glutathione-S-transferase (GST). It has been reported that some compounds, once transformed into glutathione S-conjugates, enter the mercapturic acid pathway whose end products are highly reactive and toxic for the cell responsible for their production. The cytotoxicity of these GSH conjugates depends essentially on GST and gamma-glutamyl transferases (γGT), the enzymes which initiate the mercapturic acid synthesis pathway. Numerous studies support the view that the expression of GST and γGT in cancer cells represents an important factor in the appearance of a more aggressive and resistant phenotype. High levels of tumor GST and γGT expression were employed to selectively target tumor with GST- or γGT-activated drugs. This strategy, explored over the last two decades, has recently been successful using GST-activated nitrogen mustard (TLK286) and γGT-activated arsenic-based (GSAO and Darinaparsin) prodrugs confirming the potential of GSH-conjugates as anticancer drugs.

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Section: Glutathione S-derivatives Activated By γGt and Peptidasesmentioning

confidence: 99%

Glutathione S-conjugates as prodrugs to target drug-resistant tumors

Ramsay

Dilda

2014

Front. Pharmacol.

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“…Glutathione is catabolized by the enzyme g-glutamyl transpeptidase, which transfers the residue of glutamate to a-amino acid producing a g-glutamyl-amino acid and Cys-Gly 9 . This dipeptide can promote oxidative conditions, especially in the presence of transition metal ions, such as Fe 3+ and Cu 2+ , eliciting the generation of a reactive species of oxygen [10][11][12][13][14] . Thus Cys-Gly, which has also been reported as having a signaling function [15][16][17] , can intervene in the processes responsible for the alteration of the redox status of protein cysteine residues [18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Purification and characterization of a Cys-Gly hydrolase from the gastropod mollusk,Patella caerulea

Cappiello

Spinelli

Mormino

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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A magnesium-dependent cysteinyl-glycine hydrolyzing enzyme from the gastropod mollusk Patella caerulea was purified to electrophoretic homogeneity through a simple and rapid purification protocol. The molecular masses of the native protein and the subunit suggest that the enzyme has a homohexameric structure. Structural data in combination with kinetic parameters determined with Cys-Gly and compared with Leu-Gly as a substrate, indicate that the purified enzyme is a member of the peptidase family M17. The finding that an enzyme of the peptidase family M17 is responsible also in mollusks for the breakdown of Cys-Gly confirms the important role of this peptidase family in the glutathione metabolism. KeywordsGlutathione metabolism, leucyl aminopeptidase inhibition, parasitic infections, peptidase family M17 History

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