Role Of Gamma-glutamyl Transferase Research Articles

Role of Gamma Glutamyl Transferase in the Diagnosis of Common Bile Duct Stones

Role of Gamma Glutamyl Transferase in the Diagnosis of Common Bile Duct Stones

Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease.

Background: Patients with primary sclerosing cholangitis (PSC) frequently have co-ocurring ulcerative colitis (UC) and develop colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Understanding the molecular and microbial basis for differences between these two patient groups and how these vary across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (ileum n = 7, caecum n = 7, rectum n = 7), UC (ileum n = 9, caecum n = 10, rectum n = 10) and healthy controls (ileum n = 11, caecum n = 9, rectum n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

Gamma-glutamyltransferase predicts macrovesicular liver graft steatosis – an analysis of discarded liver allografts in Finland

Objective Liver-transplantation activity is limited by the shortage of grafts. Donor-liver macrovesicular steatosis predisposes to ischemia-reperfusion injury and is associated with reduced graft survival. The increasing prevalence of fatty-liver disease underlines the importance of identifying macrovesicular steatosis in potential donor livers. We analyzed liver grafts discarded for transplantation, and particularly the role of gamma-glutamyltransferase (GGT) in predicting graft steatosis. Methods One-hundred sixty rejected cadaveric-donor liver grafts were studied. Donor selection was based on clinical data, and macroscopic graft inspection. Discarded grafts were biopsied at procurement of non-liver organs. Results The most common reasons for discarding the graft were abnormal liver tests, ultrasound-verified steatosis and history of harmful alcohol use. GGT correlated moderately with macrovesicular steatosis (r = 0.52, p < 0.001), but poorly with microvesicular steatosis (r = 0.36, p < 0.001). Increased correlation between GGT and macrovesicular steatosis was observed among alcohol abusers (r = 0.67, p < 0.001). Area under the curve (AUC) of GGT for predicting >30% macrovesicular steatosis was 0.79 (95% CI 0.71–0.88), and for >60% steatosis, 0.79 (95% CI 0.68–0.90). The optimal GGT-cut off for detecting >30% and >60% macrovesicular steatosis were, respectively, 66 U/L (sensitivity 76% and specificity 68%) and 142 U/L (sensitivity 66% and specificity 83%). Among alcohol users, a GGT value >90 U/L showed 100% sensitivity for >60% macrovesicular steatosis. AUC for GGT in predicting fibrosis Stages 2–4 was 0.82 (95% CI 0.71–0.92, p < 0.001, optimal cut off 68, sensitivity 92%, specificity 61%). Conclusions Abnormal liver values, steatosis and harmful alcohol use were the main reasons for discarding liver-graft offers in Finland. GGT proved useful in predicting moderate and severe liver graft macrovesicular steatosis.

Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease

Background: Primary sclerosing cholangitis (PSC) is a disease of the bile duct and liver. However, patients frequently have co-morbidities including inflammatory bowel disease (IBD) and colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Further, clinical and immunological features, and involved intestinal sites differ between PSC/UC and UC. Understanding the molecular and microbial basis for differences in cancer risk between these two patient groups and how these differ across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (n = 8), UC (n = 10) and healthy controls (n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC and host-microbiome associations. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

The Role of Oxidative Stress and Antioxidants in Occurrence of Myocardial Infarction and Chronic Heart Failure

Abstract Oxidative stress is one of the most important mechanisms of cardiovascular diseases, especially in heart failure. Mitochondrial dysfunction and inflammation play a major role in formation of free radicals and antioxidants. The association between oxidative stress, telomere biology and cell senescence plays the key role in cardiovascular pathology development. The paper considers role of pro-oxidant and antioxidant enzymes in heart pathology development. Specifically, the role of such antioxidant enzymes as glutathione peroxidase 3, catalase, and superoxide dismutase is described. The role of gamma-glutamyl transferase is emphasized as its activity increases significantly in cases of heart failure, coronary heart disease, stroke, arterial hypertensions, and arrhythmias. This article is a literature review of the effect of such antioxidants as alpha-tocopherol, ubiquinone, uric acid, and triiodothyronine on development of heart failure and myocardial infarction. A decrease in triiodothyronine concentration is a risk factor for coronary heart disease. High uric acid values in patients with myocardial infarction upon admission to the hospital are associated with a high risk of sudden death. The influence of such minerals such as zinc, copper, magnesium, selenium, potassium, sodium, calcium, and iron on heart failure development has been analyzed. The role of ceruloplasmin as an independent predictor of acute and chronic cardiac disorders cardiac events, mortality, and bad prognosis in patients with heart failure and myocardial infarction is examined. The authors demonstrate the influence of inflammation on heart failure development as well as association of inflammation with oxidative stress.

Role of Gamma Glutamyltransferase and Alkaline Phosphatase Assay in Enzymatic Panel for Hepatobiliary Function in Patients Attending Kibungo Hospital, Rwanda

Background: Liver complications show specific processes like hepatoxicity associated with drugs, primary neoplasm, or hepatotropic virus infections. Different markers based on laboratory testing help to diagnose and monitor liver related conditions. Mostly used tests are classed in a set known as hepatic panel or liver profile mainly consisting of body enzymes.Objective: The objective of the present study was to ascertain the role of gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP) assay in enzymatic panel for hepatobiliary function assessment among patients attending Kibungo hospital.Methods: Two hundred twenty-five clients were included in the study. Demographic data were collected from December 2016 to March 2017. Blood sera were also collected and tested for serum GGT and ALP levels. Statistical package for social sciences (SPSS) was used in data analysis.Results: Seventy-four point seven per cent of clients had normal GGT whereas 63.1% had normal ALP. The 0.9% of clients comprised low levels of ALP. The means were 53 and 153 U/L for GGT and ALP, respectively. Fifty per cent of alcohol consumers’ population had elevated GGT and ALP. An increase of 69.2 and 61.5% for GGT and ALP, respectively was observed in smokers’ population. The subpopulation of hepatitis C virus (HCV) was the most with elevated GGT and ALP levels. In HIV population, serum GGT and ALP were raised at 31.1 and 37.8%, respectively. In fact, hepatitis B virus (HBV), HCV, and HIV patients are clinically considered as immuno-compromised people. Alcohol consumption and smoking were also found to increase GGT and ALP concentrations. In addition, GGT and ALP levels were simultaneously elevated in 19.6% of the clients, indicating the frequency of cholestatic liver disease.Conclusion: Elevated GGT and ALP revealed the occurrence of cholestasis among study participants due to factors that elevate serum GGT and ALP levels as a result of dysfunctional liver conditions. In hospital laboratories, GGT and ALP should always be included in the panel of tests for screening and bio-monitoring liver related conditions in Rwanda.

Gamma glutamyltransferase and risk of dementia in prediabetes and diabetes

Diabetes is associated with cognitive impairment and greater risk for dementia, but the role of gamma-glutamyltransferase (γ-GT) in dementia has not been elucidated. We determined incident dementia including Alzheimer’s disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants were diagnosed as having dementia. Higher serum γ-GT was associated with increased risk of dementia (HR = 1.22, 95% CI = 1.20–1.24), and had a strong positive association with early onset dementia (HR = 1.32, 95% CI = 1.24–1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR = 1.82, 95% CI = 1.78–1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR = 1.94, 95% CI = 1.84–2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population.

Role of gamma glutamyl transferase as a diagnostic marker of metabolic syndrome

Role of gamma glutamyl transferase as a diagnostic marker of metabolic syndrome - IJN- Print ISSN No: - 2581-8236 Online ISSN No:- 2581-916X Article DOI No:- 10.18231/j.ijn.2019.018, IP Indian Journal of Neurosciences-IP Indian J Neurosci

Role of Gamma Glutamyl Transferase in the Diagnosis of Metabolic Syndrome in Patients with Hypothyroidism

Role of Gamma Glutamyl Transferase in the Diagnosis of Metabolic Syndrome in Patients with Hypothyroidism

Gamma Glutamyltransferase and Risk of Dementia in Normal, Prediabetes, and Diabetes Populations—A Nationwide Cohort Study with 6.5 Million People

Diabetes is associated with cognitive impairment and increases risk of dementia, but until now the role of gamma-glutamyltransferase (γ-GT) in dementia has not been studied. We thus investigated the impacts of γ-GT and glycemic status on incident dementia in a nationwide cohort study. We determined incident dementia including Alzheimer’s disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants (5.4%) were diagnosed as having dementia at a mean age of 76.5 years. Higher serum γ-GT was associated with increased risk of dementia (HR=1.22, 95% CI=1.20-1.24), and had a strong positive association with early onset dementia (HR=1.32, 95% CI=1.24-1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR=1.82, 95% CI=1.78-1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR=1.94, 95% CI=1.84-2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population. Disclosure E. Han: None. M. Lee: None. Y. Cho: None. B. Lee: None. C. Ahn: None. B. Cha: None. Y. Lee: None.

Association of serum gamma-glutamyltransferase and C-reactive proteins with neuromyelitis optica and multiple sclerosis

BackgroundMany studies have demonstrated that serum gamma glutamyltransferase (GGT) within normal range might be an early marker of oxidative stress. However the role of GGT in neuromyelitis optica (NMO) and multiple sclerosis (MS) is unknown. MethodsWe assessed the correlations among GGT and C-reactive protein (CRP) levels, as well as clinical characteristics of NMO and MS. Serum GGT and CRP levels were measured in 106 NMO patients, 87 MS patients, 79 patients with non-inflammatory neurological diseases (Parkinson disease) and 80 healthy controls (HC). Clinical parameters, blood-brain barrier (BBB) index and Delpech index of MS and NMO were also investigated. ResultsWe found that NMO patients had higher serum GGT and CRP levels within their normal ranges compared to MS, PD, healthy controls. NMO patients exhibited significantly higher EDSS scores than MS patients. The BBB index in NMO patients was significantly higher than that in MS patients. Significant correlations existed between serum GGT and CRP levels and EDSS scores, BBB index in NMO and MS patients. ConclusionElevated GGT and CRP levels within their normal ranges in NMO and MS may be associated with inflammatory response, oxidative stress and BBB disturbance in the diseases. Further study into the underlying pathophysiology of this relationship is warranted.

Serum gamma glutamyl transferase levels in association with lipids and lipoproteins in type2 diabetes mellitus

Background: Serum gamma glutamyl transferase is widely used as a marker for alcohol induced liver disease. Recently it has gained importance due to its role in type2 diabetes mellitus. A raised serum gamma glutamyl transferase level indicates hepatic steatosis and visceral fat deposition, leading to insulin resistance and diabetes. In the present study we examined the association between serum gamma glutamyl transferase levels with lipids and lipoproteins in diabetes mellitus. Methods: The study was carried out on 50 subjects with type 2 diabetes mellitus and compared with 50 age and sex matched healthy controls attending outpatient department of general medicine, Narayana medical college, Nellore. Serum gamma glutamyl transferase was measured by calorimetric kinetic assay. Fasting blood sugar was measured by glucose oxidase method using automated analyzer. Serum triglycerides, total cholesterol and high density lipoprotein are measured by standard enzymatic procedures and low density lipoprotein by Friedwald equation. Results: Serum gamma glutamyl transferase levels in diabetic cases were significantly elevated compared to normal healthy controls (P <0.001). There was a positive correlation between gamma glutamyl transferase, lipids and low density lipoprotein and inverse correlation with high density lipoprotein (r = -0.298). Conclusion: Our results suggest a possible role of gamma glutamyl transferase in the pathophysiology and progression of type 2 diabetes mellitus.

The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

BackgroundBlood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits). MethodsData on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N=6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy. ResultsPhenotypic correlations between alcohol intake and GGT were significant in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4–7% vs. 1–2% of the variance in GGT respectively). ConclusionsIn this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations.

Pathomechanism of Insulin Resistance in Men with Central Obesity: Correlation of GGT, GPx, hs-CRP and Plasma Total Cysteine

BACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed.METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC &gt;100 cm, without fatty liver; Group IV: WC &gt;100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed.RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV.CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC &gt;100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.KEYWORDS: GGT, hs-CRP, GPx, tCys, HOMA-IR, insulin resistance

The role of gamma-glutamyltransferase in malignant transformation and prognosis of ovarian cancer.

e16524 Background: Gamma-glutamyltransferase (GGT) – a membrane bound enzyme crucially involved in the cell’s detoxification pathway and apoptotic balance – is involved in tumor development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multi-center study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n = 567) and borderline tumor of the ovary (BTO, n = 67). GGT serum levels were associated with clinico-pathological parameters and uni- and multivariate survival analyses were performed.Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. Results: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 [38.24] U/L) than in patients with BTO (20.01 [12.78] U/L, p = 0.01). High GGT serum levels were associated with advanced FIGO stage (p&lt;0.001) and with worse overall survival in univariate (p &lt; 0.001) and multivariable analysis (p=0.02, HR 1.2 [1.1-1.5]). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumor tissue and observed an association between these two parameters (p = 0.03). Conclusions: High pre-therapeutic GGT serum levels are associated with advanced tumor stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. GGT expression in ovarian cancer tissue is reflected in GGT serum levels.

Role of gamma-glutamyl transferase (GGT) in diagnosis of impaired glucose tolerance and metabolic syndrome: A prospective cohort research from the Kerman Coronary Artery Disease Risk Study (KERCADRS)

AimsThe important role of raised serum gamma-glutamyl transferase (GGT) for predicting diabetes mellitus and insulin resistance is clear; however relationship between increased level of GGT and impaired glucose tolerance (IGT) is now hypothesized. We aimed to show the importance of GGT measurement in diagnosis of IGT. Materials and methodsTwo hundred persons were randomly selected from the Kerman Coronary Artery Disease Risk Study (KERCADRS), as a population-based study. All participants underwent GGT analysis test, besides measuring risk factors and components of metabolic syndrome (MS). ResultsThe increase in GGT was correlated with increased prevalence of IGT and MS and its different components. In multivariable analysis, a high GGT was positively associated with the presence of IGT after adjustment for age, sex and MS diagnostic criteria. The area under curve (AUC) for GGT was 0.722 for discriminating IGT from normal condition, and 0.847 for discriminating MS from normal status. In ROC curve analysis, the optimal cut-off value for GGT to discriminate IGT from normal condition was 20.5IU with the sensitivity of 71.6% and the specificity of 66.1%. The best cutoff value for GGT to discriminate MS from normal condition was also 16.5IU with the sensitivity and specificity of 78.4% and 78.4%, respectively. ConclusionThe measuring GGT can be a sensitive method for early diagnosis and predicting IGT and MS from normal condition. Because this diagnostic test is a low-cost, highly sensitive, accurate and frequently used laboratory test, its measurement is recommended as a useful marker of both IGT and MS.

Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase

Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7 ± 5.8 years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.

Gamma-Glutamyl Transferase: The Silent Partner?

ABSTRACTGlutathione is one of the most abundant proteins in vivo involved in maintaining cellular homeostasis and is essential for the regulation of oxidant stress. Gamma-Glutamyl transferase (GGT) is the first enzyme of the gamma glutamyl cycle that regulates the antioxidant glutathione, hence it is a critical enzyme in glutathione homeostasis. Recent findings have indicated upregulation of GGT in inflammation, increasing antioxidant defence whilst potentially driving leukotriene-induced inflammation. GGT is a marker of future comorbid diseases consistent with inflammation (and oxidative stress) as a key central pathophysiological process. COPD reflects several distinct pathological phenotypes. Inflammation (and hence oxidative stress) is influenced by other factors such as bacterial colonisation and exacerbations. The increased incidence of other co-morbid conditions with systemic inflammation suggests that common pathophysiological processes are responsible. Active oxidant stress and hence the role of GGT may play a role in these processes. Future studies of systemic and local GGT function and genotypes in well characterised patients may lead to a better understanding of the processes involved and hence the development of new treatment strategies.

Role of gamma-glutamyltransferase in the homeostasis of glutathione during oxidative and nitrosative stress.

Glutathione (GSH) is an important and abundant antioxidant in most cells, including cancer cells. The GSH level can be significantly reduced during oxidative and nitrosative stress, and GSH depletion is an early step in apoptosis. As most cells have no uptake mechanism of GSH, they depend on resynthesis to prevent cell death. A limiting factor in cellular GSH synthesis is the availability of cyst(e)ine (for recent reviews, see [1,2]). During tumor progression cancer cells tend to develop invasive and metastatic growth and resistance to therapy. They also show metabolic alterations that are termed loss of differentiation, and frequently these changes include increased resistance towards oxidative and nitrosative stress [3,4]. It has been shown that GSH protects tumor cells against oxidative stress in liver microvasculature [5] and that tumor cells with elevated GSH or ability to resynthesise GSH possess a higher invasive potential [4,6]. NO is highly tumoricidal in the presence of H2O2 [6,7], and these agents appear to be part of a natural defence towards metastatic growth [8]. GSH plays an important role in the protection of tumor cells against NO mediated apoptosis [9,10] and intracellular GSH will therefore contribute to the mechanisms of tumor cell survival during metastatic growth. The enzyme γ-glutamyltransferase (GGT) initiates the breakdown of extracellular glutathione by hydrolysing the γ-glu-cys bond in GSH. The remaining part, cys-glu, is then hydrolysed by peptidases. Cellular uptake of the amino acids will thus provide the monomers needed for GSH biosynthesis [11] and it has been suggested that GGT has significant importance for GSH homoestasis when the level of cyst(e)ine is reduced [12–14]. Fibroblasts requiring cysteine can grow in cysteine-free medium if supplemented with GSH [12,15]. Cells cultivated in vitro have access to surplus amounts of cystine

Age-dependent removal of circulating glutathione by rat liver: Role of gamma-glutamyl transferase

Total gamma-glutamyl transferase (GGT) activity was found to be 93% greater in the liver of old (60 weeks) rats compared to young (12 weeks) adult animals. In vitro perfused livers of old animals also had shown 92% greater capacity to hydrolyze glutathione (GSH) from the circulation. GSH removal was fully dependent on GGT activity. It increased 50% when glycylglycine was added to the perfusion buffer. There was a positive and highly significant correlation (r=0.984; p<0.005) in the liver of old rats between total GGT activity and the ability of the liver of these animals to remove GSH from the circulation. Results presented here point to a physiological and functional significance to the age-related differences in total liver GGT.