γ‐Glutamyltransferase‐dependent prooxidant reactions: A factor in multiple processes

Dominici, Silvia; Paolicchi, Aldo; Lorenzini, Evelina; Maellaro, Emilia; Comporti, Mario; Pieri, L; Minotti, Giorgio; Pompella, Alfonso

doi:10.1002/biof.5520170118

Cited by 57 publications

(49 citation statements)

References 35 publications

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“…We measured the concentration of cysteinylglycine in plasma because it is an important component of the cysteine-glutathione pathway. It has been reported that cysteinylglycine oxidizes plasma low-density lipoprotein and causes oxidative damage to DNA [35,36,37,38]. These findings suggest that cysteinylglycine may have a role in the pathophysiology of CVD and cancer.…”

Section: Discussionmentioning

confidence: 60%

Serum Folate Is Significantly Correlated with Plasma Cysteine Concentrations in Healthy Industry Workers

Mansoor¹,

Hervig²,

Stakkestad³

et al. 2011

Ann Nutr Metab

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Background: A low concentration of serum folate is associated with an increased risk of cardiovascular disease. Extracellular cysteine is involved in aging, cancer and cardiovascular disease. The relationship between serum folate and plasma cysteine is poorly understood. Therefore, we investigated this relationship in industry workers, whose health has economic implications. Methods: The concentration of serum folate was determined by the Access ImmunoAssay System Sanofi Pasteur. Plasma cysteine and homocysteine were measured by an ion-pair HPLC method. The concentrations of serum triglycerides were determined by an enzymatic colorimetric method. Results: We detected a positive correlation between the concentration of serum folate and plasma cysteine, whereas the concentration of serum folate was negatively correlated with plasma homocysteine and serum triglycerides. In a multiple regression analysis with adjustment for age, BMI and smoking, serum folate as the dependent variable exhibited a strong relationship with plasma cysteine, and a negative relationship with plasma homocysteine and serum triglycerides. Conclusion: We observed significant correlations between serum folate, plasma cysteine and serum triglyceride concentrations in industry workers, implying that folate may modulate key aspects of the body’s cysteine and lipid metabolism.

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Section: Discussionmentioning

confidence: 60%

Serum Folate Is Significantly Correlated with Plasma Cysteine Concentrations in Healthy Industry Workers

Mansoor¹,

Hervig²,

Stakkestad³

et al. 2011

Ann Nutr Metab

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“…This cysteinyl-glycine is one of the most reactive thiol compounds that possess very high physiological activity, and it has been reported that this particular thiol can reduce oxygen under normal physiological conditions by reducing ferric iron Fe 3ϩ into ferrous Fe 2ϩ (Stark et al, 1993). This process is generally known as the iron redox-cycling process and, as a consequence, produces reactive oxygen species (ROS) that subsequently facilitate an oxidative reaction (Dominici et al, 2003(Dominici et al, , 2005. The highest level of GGT activity is the outer surface of the microvillus membrane (brush border) in the proximal tubule of the kidney (Meister and Tate, 1976;Marathe et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Yamamoto¹,

Watanabe²,

Hiratake³

et al. 2011

J Pharmacol Exp Ther

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GGsTop [2-amino-4-{[3-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid], is a novel, highly selective, and irreversible ␥-glutamyl transpeptidase (GGT) inhibitor with no inhibitory activity on glutamine amidotransferases. In this study, we investigated the effects of treatment with GGsTop on ischemia/reperfusion-induced renal injury in uninephrectomized rats. Ischemic acute kidney injury (AKI) was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated AKI rats markedly decreased at 1 day after reperfusion. Treatment with GGsTop (1 and 10 mg/kg i.v.) 5 min before ischemia attenuated the ischemia/reperfusion-induced renal dysfunction in a dose-dependent manner. Histopathological examination of the kidney of AKI rats revealed severe renal damage, which was significantly suppressed by the GGsTop treatment. In renal tissues exposed to ischemia/reperfusion, GGT activity was markedly increased immediately after reperfusion, whereas renal superoxide production and malondialdehyde level were significantly increased 6 h after reperfusion. These alterations were abolished by the treatment with GGsTop. In addition, renal glutathione content was decreased by the 45-min ischemia, but its level was markedly elevated by the GGsTop treatment. Our results demonstrate that the novel and highly selective GGT inhibitor GGsTop prevents ischemia/ reperfusion-induced AKI. The renoprotective effect of GGsTop seems to be attributed to the suppression of oxidative stress by inhibiting GGT activation, thereby preventing the degradation of glutathione.

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“…The pro-oxidant cysteinylglycine has been suggested to promote the reduction of Fe 3+ to Fe 2+ (21) and also to lead to lipid peroxidation (22). Only a few studies have investigated associations of cysteinylglycine with chronic disease and have provided some evidence for increased risk of heart disease (23) and breast cancer (24) with increased serum cysteinylglycine.…”

Section: Introductionmentioning

confidence: 99%

Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers,

Miranti

Freedman

Weinstein

et al. 2016

The American Journal of Clinical Nutrition

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Background: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. Objective: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the AlphaTocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. Design: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. Results: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. Conclusions: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.Am J Clin Nutr 2016;104:686-93.

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γ‐Glutamyltransferase‐dependent prooxidant reactions: A factor in multiple processes

Cited by 57 publications

References 35 publications

Serum Folate Is Significantly Correlated with Plasma Cysteine Concentrations in Healthy Industry Workers

Serum Folate Is Significantly Correlated with Plasma Cysteine Concentrations in Healthy Industry Workers

Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers,

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