γ-GTP Activity Research Articles

Mild-to-Moderate Malnutrition Alters Glutathione, Gamma-Glutamyl-Transpeptidase and Glycine Uptake in Small Intestinal Brush-Border Vesicles of Rhesus Monkeys

Background: In India about 85% of pre-school children show evidence of mild-to-moderate malnutrition. Consequences of severe malnutrition and protein deficiency are well reported by workers but little information is available on milder forms. Methods: Mild-to-moderate protein energy malnourished (PEM) state was induced in 12 monkeys by providing 2.42 g protein and 55 kcal kg^–1 day^–1 while 12 controls were fed 4.84 g protein and 110 kcal kg^–1. After a 30–40% reduction in body weight as compared with their controls, the animals were killed and brush border membrane vesicles (BBMV) were prepared from three parts of small intestine. Purified vesicles were assayed for gamma-glutamyl-transpeptidase (GGTP), glutathione (GSH) and U-¹⁴C-glycine uptake. Results: GGTP activity increased significantly while glutathione and uptake of glycine decreased significantly in all the three parts of small intestine. On nutritional rehabilitation of 9 weeks, the activity of GGTP, GSH and in vitro uptake of glycine amino acid recovered completely. Conclusion: The results of the present study indicates that even mild-to-moderate malnutrition should not be ignored during the development state.

Increased γ-Glutamyl Transpeptidase Activity During Inflammation and its Inhibition by 6-MFA, a Metabolite Obtained from <I>Aspergillus ochraceus</I>

γ-Glutamyl transpeptidase (γ-GTP) is known to play a vital role in the turnover of glutathione and protein synthesis. Hence, it is presumed that changes in the activity of γ-GTP in inflamed tissue itself might occur as both catabolic and anabolic processes are activated simultaneously in inflammation. The aim of this study was to determine γ-GTP activity in oedematous and granulomatous tissues in carrageenin-induced hind-paw oedema and cotton-pellet granuloma, respectively, in rats. In the time course study, maximum γ-GTP activity was observed in oedematous tissue at 4h after carrageenin injection and in granulomatous tissue on Day 7 after cotton-pellet implantation. Treatment with 6-MFA significantly inhibited the increase in γ-GTP activity in both oedematous and granulomatous tissues. The results suggest that the measurement of γ-GTP activity in inflammation may serve as a sensitive biochemical marker for evaluation of the in-vivo anti-inflammatory activity of drugs.

γ-Glutamyl transpeptidase as a possible marker of Sertoli cells in fish testes for studies of xenoestrogens

Estrogenic chemicals are known to have marked effects on the reproductive system of male fish. Finding useful markers of reproductive effects are therefore of great importance and interest. γ-Glutamyl transpeptidase (γ-GTP) is a possible marker of Sertoli cells in testes of fish. In the present study we have examined the relationship between the activity of γ-GTP and the histological structure of the Sertoli cells in testes of five fish species (guppy, Poecilia reticulata; platyfish, Xiphophorus maculatus; eelpout, Zoarces viviparus; rainbow trout, Oncorhynchus mykiss; flounder, Platichthys flesus). In general we found that the more distinct the Sertoli cells the higher the activity of γ-GTP.

Effect of N‐Acetylsphingosine (C2) and the Ceramidase Inhibitor (1S,2R)‐D‐erythro‐2‐(N‐myristoylamino)‐1‐phenyl‐1‐propanol on the Regulation of Sertoli Cell Function

In the present study, a possible role of ceramide in the regulation of Sertoli cell function was investigated. Intracellular ceramide levels were increased by adding N-acetylsphingosine (C2) or by inhibiting ceramidase with (1 S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (MAPP). Cultured Sertoli cells were stimulated for 3 days with different doses of C2, MAPP, and their corresponding inactive analogs. The effect of these drugs was evaluated along four well-known Sertoli cell parameters: lactate and transferrin secretion, gamma-glutamyl transpeptidase (gamma-GTP) activity, and estradiol production. C2 and MAPP increased lactate production and decreased transferrin secretion. The inactive analogs did not produce any effect. In FSH (follicle-stimulating hormone)-stimulated cultures, C2 and MAPP produced a further increment in lactate production and decreased FSH-stimulated transferrin secretion. No effect was observed under basal or FSH-stimulated gamma-GTP activity, and both treatments decreased estradiol production in response to FSH. Results obtained in dbcAMP (dibutyryladenosine 3':5'-cyclic monophosphate)-stimulated cultures suggest that the observed effects of ceramide on transferrin secretion are secondary to a decrease in cAMP production, whereas the effects of ceramide on lactate and estradiol productions are post-cAMP formation regulatory events. In summary, our results show that ceramide can regulate Sertoli cell function. Similar to what has been observed for other signaling molecules, ceramide can interact with the FSH-dependent pathway, but the precise steps involved in this interaction are still unknown.

Involvement of Renal γ-Glutamyltranspeptidase in Differences in the Renal Uptake of Mercuric Mercury by Male and Female Mice of Various Strains and Ages

Involvement of renal γ-glutamyltranspeptidase (γ-GTP) in differences in the renal uptake of Hg2+ by male and female mice of various ages was examined using five strains of mice, namely, BALB/cA, C57BL/6N, CBA/JN, C3H/HeN and ICR. We observed strain-related and gender-related differences in the renal accumulation of Hg<2+> 30min after the administration of mercuric chloride (1μmol/kg, s.c.). Renal γ-GTP activity also varied among the tested strains, and the activity in males was about twice that in females. A significant correlation was recognized between renal γ-GTP activity and the renal accumulation of Hg<2+>. Both renal uptake of Hg<2+> and renal γ-GTP activity increased gradually with age in male ICR mice from 2 to 8 weeks after birth but remained relatively constant in ICR females. Significant gender-related differences in both renal accumulation of Hg<2+> and γ-GTP activity were observed 4 weeks after birth and thereafter. Castration of male ICR mice decreased both renal accumulation of Hg<2+> and γ-GTP activity to the levels in females. Injection of testosterone increased both renal accumulation of Hg<2+> and γ-GTP activity in castrated male mice and in normal female mice to the levels in control male mice. These results suggest that strain-related, gender-related and age-related differences in the renal accumulation of Hg<2+> in mice might be due to differences in renal γ-GTP activity and, furthermore, that renal γ-GTP activity might be controlled, at least to some extent, by testosterone.

Changes in the hepatic glutathione peroxidase redox system produced by coplanar polychlorinated biphenyls in Ah-responsive and -less-responsive strains of mice: mechanism and implications for toxicity

The alteration in hepatic glutathione peroxidase (GPx) produced by polychlorinated biphenyls (PCBs) was studied in vivo in aryl hydrocarbon (Ah)-responsive C57BL and -less-responsive DBA strains of mice. 3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126), one of the high-affinity ligands for the Ah receptor, significantly reduced Se-dependent GPx activity in C57BL mice, but not in DBA mice. A reduction in activity in C57BL mice was also observed following treatment with a high dose of 3,3′,4,4′-tetrachlorobiphenyl with lesser affinity for the Ah receptor than PCB 126, but not by 2,2′,5,5′-tetrachlorobiphenyl, a low-affinity ligand. To assess the effects on GPx in the liver, the content of reduced glutathione (GSH), an obligate co-factor for GPx, and the activity of two enzymes, γ-glutamyl transpeptidase ( γ-GTP) and glutathione reductase (GR), which play a role in supplying GSH were determined after PCB treatment. The results showed that although the hepatic activity of γ-GTP and GR was affected differently by PCB 126, the content of GSH was slightly increased rather than reduced in both strains of mice. The activity of non-Se-dependent GPx, which is due to the catalysis by some isozymes of glutathione S-transferase (GST), was significantly increased only in C57BL mice by PCB 126 treatment. Immunoblot analysis demonstrated that the induction of the class θ GST, which is a potent reducer of peroxides (Hiratsuka et al., 1995. Biochem. Biophys. Res. Commun. 212, 743) reflects the enhancement of the above activity. These results suggest that (i) the PCB-induced reduction in Se-dependent GPx activity is mediated by a mechanism involving the Ah receptor; and (ii) a concomitant increase in the class θ GST partially rescues the Ah-responsive mice from coplanar PCB-induced oxidative stress.

Regulation of gamma-glutamyl transpeptidase activity by Ca(2+)- and protein kinase C-dependent pathways in Sertoli cells.

gamma-Glutamyl transpeptidase (gamma-GTP) activity in Sertoli cells can be stimulated by FSH. This cAMP-dependent metabolic event can be enhanced when Sertoli cells are co-cultured with germ cells, suggesting that different signal transduction pathways may be involved in the regulation of gamma-GTP activity. In this study we examined the participation of Ca(2+)- and protein kinase C (pkC)-dependent signal transduction pathways in the regulation of basal and FSH-stimulated gamma-GTP activity. Under basal conditions, the increase in extracellular Ca2+ concentration or the addition of the Ca2+ ionophore 4Br-A23187 produced a decrease in gamma-GTP activity. Conversely, blockage of voltage-dependent Ca2+ channels with verapamil or nifedipine or inhibition of Ca(2+)-calmodulin dependent processes with trifluoperazine resulted in an increase in gamma-GTP activity. To study the role of a pkC-dependent pathway the effects of low doses of staurosporine were evaluated. Under these experimental conditions an increase in gamma-GTP activity was observed. It was then investigated whether these signal transduction pathways could interact with the FSH-stimulated cAMP-dependent pathway to regulate gamma-GTP activity. Increase in extracellular Ca2+ concentration, the addition of 4Br-A23187 or the blockage of voltage-dependent Ca2+ channels did not modify FSH-stimulated gamma-GTP activity. However, staurosporine produced an additional increase in FSH-stimulated gamma-GTP activity and this effect was also observed when cells were stimulated with dbcAMP. In summary, our data are consistent with an inhibitory role of Ca(2+)-calmodulin- and pkC-dependent pathways in the regulation of basal gamma-GTP activity. Similar to what has been shown for other Sertoli cell parameters, a pkC-dependent pathway can interact with the FSH-stimulated cAMP-dependent pathway. The precise steps involved in this interaction are still unknown.

Elevation of glutathione and related enzyme activities in high-grade and metastatic extremity soft tissue sarcoma

Glutathione is a free radical scavenger implicated in the chemoresistance of certain tumors. As treatment with chemotherapy has added little to improved survival in adult soft tissue sarcoma and little is known concerning the mechanisms of chemoresistance in sarcoma, we studied concentrations of glutathione (nmol/mg protein) and activities of gamma-glutamylcysteine synthetase (GCS; nmol/mg protein/h) and gamma-glutamyl transpeptidase (GGTP; U/mg protein) in extremity soft tissue sarcoma. Tumor specimens (n = 65) were frozen in liquid nitrogen at the time of resection. Fourteen low-grade tumors, 40 high-grade tumors, and 11 pulmonary metastases were analyzed. Glutathione concentrations and GGTP activity were significantly lower in low-grade (3.97 +/- 0.7 nmol/mg protein and 1.07 +/- 0.2 U/mg protein) than in high-grade (8.98 +/- 1.2 nmol/mg protein, p < 0.001; 2.10 +/- 0.4 U/mg protein, p < 0.002) tumors and pulmonary metastases (10.05 +/- 1.8 nmol/mg protein, p < 0.008; 3.14 +/- 2.8 U/mg protein, p < 0.04). While GCS activity was lower in low-grade (0.81 +/- 0.3 nmol/mg protein/h) than high-grade (1.49 +/- 0.5 nmol/mg protein/h) tumors and pulmonary metastases (1.03 +/- 0.2 nmol/mg protein/h), these differences were not significant. In those patients with a high-grade tumor presenting with a local recurrence, glutathione levels were higher in those patients who had received preoperative doxorubicin-based chemotherapy (9.25 +/- 1.7 nmol/mg protein; n = 7) than in those who had no preoperative chemotherapy (4.71 +/- 3.1 nmol/mg protein; n = 4, p = 0.08). In extremity soft tissue sarcoma, glutathione concentration and GGTP activity are significantly elevated in patients with high-grade and metastatic sarcomas. In addition, there is a trend for increased glutathione levels in tumors previously exposed to doxorubicin-based chemotherapy. Glutathione may play a role in soft tissue sarcoma chemoresistance.

Membrane Proteases in Human Malignant Lymphomas.

The activities of membrane-bound proteases: γ-glutamyltranspeptidase (γ-GTP), microsomal alanyl aminopeptidase (mAAP, formerly APM), glutamyl-aminopeptidase (EAP, formerly APA) and dipeptidyl peptidase IV (DPP-IV) -were examined in 11 cases with non-Hodgkin's malignant lymphomas (NHL), in 7 cases with Hodgkin's disease (HD) and 8 cases with reactive follicular hyperplasia (RFH) by means of enzyme histochemical methods. The results indicated that there was correlation between grade malignancy of NHL and γ-GTP activity: high grade NHL displayed strong γ-GTP activity, whereas low grade NHL showed weak activity. HD also showed various patterns of γ-GTP activity. Of 7 HD examined, 4 showed strong γ-GTP activity and 3 other were slightly positive. The lymphoid cells in RFH and neoplastic cells in NHL and HD failed to exhibit mAAP- and EAP activities. The activities of these enzymes were seen in stromal cells. Variable numbers of small mature lymphocytes in RFH and in malignant lymphomas showed dot-like DPP-IV activity. Thus, the study of γ-GTP activity may be a valuable diagnostic feature in the distinction between NHL of low and high grade malignancy and may prove to be a useful marker with which to predict drug- and irradiation resistance. Moreover, mAAP- and EAP pattern in the lymphoid cells may be useful in defining in lymph nodes the metastatic tumour cells with strong activities of these enzymes.

An In Vitro Model of the Blood-Brain Barrier: The Response of Madin-Darby Canine Kidney Cells to Triethyl Tin

The development of a cell culture model which simulates the properties of the blood–brain barrier (BBB) is necessary for the detection of neurotoxic chemicals that can disrupt the barrier, and to provide a more “risk relevant” in vitro screening battery. The present study evaluates the Madin-Darby canine kidney (MDCK) epithelial cell line for this purpose. Changes in electrical resistance and enzyme activities were correlated in confluent MDCK cells exposed to the neurotoxic metal, triethyl tin (TET). Concentrations of TET (0.001–10μM) were established that produced depression in electrical resistance of the MDCK cells after exposure for 8 hours or caused fluorescein leakage after exposure for 72 hours. Confluent cultures of MDCK cells were then exposed to these concentrations of TET and assayed after exposure for 24 hours and 72 hours for changes in those enzymes common to both epithelial and cerebral endothelial cells. The results indicated that increased alkaline phosphatase (APP), γ-glutamyl transpeptidase (GGTP) and superoxide dismutase (SOD) characterised the loss of electrical resistance and permeability disruption in TET-exposed MDCK confluent cultures. Relative increases in APP and decreases in GGTP activities preceded cytotoxicity, which was associated with a high SOD activity. Such enzyme changes may be predictive endpoints of barrier cell disruption by neurotoxic metals in this cell line and support the additional evaluation of the MDCK cell line as an in vitro “screen” for chemicals that disrupt the BBB.

Predictive modeling of lactoperoxidase and γ-glutamyl transpeptidase inactivation in a high-temperature short-time pasteurizer

Linear models were derived to describe the thermal inactivation of γ-glutamyl transpeptidase (GGTP) and lactoperoxidase (LP) in bovine milk in a high-temperature short-time (HTST) pilot scale pasteurizer. Integrated lethal effect (pasteurization effect; PE) was related by simple linear functions to the log 10 of the % initial activity with a power transformation of the PE values to improve linear fit. The PE values required for a 1-log reduction in GGTP and LP activity, calculated from the equation parameters were 5.46 and 26.5, respectively, suggesting that LP is considerably more heat stable than GGTP. The two linear equations were validated using data from additional trials. Greater variation was found with the LP assay as compared to the GGTP suggesting that the assay method requires improvement. These linear models can be incorporated into user-friendly software to facilitate the estimation of lethal effect achieved with other pasteurization equipment.

Enzymatic barrier protects brain capillaries from leukotriene C4

Leukotriene C4 (LTC4) increases vascular permeability in systemic, brain tumor, and ischemic brain capillaries, but not in normal brain capillaries. This study examines whether the abundance of gamma-glutamyl transpeptidase (gamma-GTP) in normal brain capillaries might act as an enzymatic barrier to vasoactive leukotrienes in the brain. Blood-brain barrier (BBB) permeability was determined by quantitative autoradiography using 14C-aminoisobutyric acid. Ischemia was produced by occluding the middle cerebral artery. Seventy-two hours after occlusion, gamma-GTP activity in ischemic brain disappeared, and LTC4 (4-micrograms total dose), which was infused into the carotid artery ipsilateral to the occlusion, selectively increased permeability, Ki, approximately twofold within core ischemic tissue and adjacent tissue, compared to vehicle alone in seven brains (15.53 +/- 6.03 vs. 7.29 +/- 3.36, p < 0.05, and 8.76 +/- 4.02 vs. 4.32 +/- 2.65, p < 0.05, respectively). No effect on BBB was seen in nonischemic brain tissue. Twenty-four hours postocclusion, gamma-GTP activity was still present, and LTC4 infusion did not increase permeability within ischemic tissue. However, inhibition of gamma-GTP with acivicin allowed LTC4 to increase permeability even 24 hours after occlusion in ischemic core and adjacent tissue compared to vehicle alone in seven brains (17.21 +/- 16.32 vs. 8.23 +/- 6.58, p < 0.05, and 11.78 +/- 7.96 vs. 4.56 +/- 1.93, p < 0.01, respectively). Acivicin almost completely blocked both the histochemical activity of gamma-GTP in brain capillaries and the metabolism of LTC4 in isolated bovine capillaries. These findings suggest that gamma-GTP may help normal brain capillaries resist the vasoactive effects of LTC4. In contrast, gamma-GTP is lost in injured brain capillaries, which allows LTC4 (in combination with other factors) to increase vascular permeability in ischemic brain and brain tumors.

Amniotic fluid digestive enzymes: Diagnostic value in fetal gastrointestinal obstructions

The diagnostic value of amniotic fluid gamma-glutamyl-transpeptidase (GGTP) and intestinal alkaline phosphatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.

Glial extracellular matrix modulates γ-glutamyl transpeptidase activity in cultured bovine brain capillary and bovine aortic endothelial cells

Glial extracellular matrix (ECM) elevated γ-glutamyl transpeptidase (γ-GTP) activity in cultured bovine brain capillary and aortic endothelial cells (BBCEC, BAEC). In particular, the ECM of glial cells cultured with the conditioned medium of BAEC (BAEC CM) dramatically elevated γ-GTP activity in BBCEC and BAEC. The ECM of glial cells cultured with BBCEC CM also had a marked effect. The ECM of 3T3 cells cultured with BAEC CM, and the ECM of glial cells cultured with 3T3 CM had no effect. Glial CM had no effect on γ-GTP activity in BBCEC and BAEC. These findings indicate that γ-GTP activity in endothelial cells (EC) is modulated by glial ECM, and that the factor of ECM that affects γ-GTP activity in EC arises from the interaction between glial cells and EC.

Thermal inactivation of gamma-glutamyltranspeptidase and Enterococcus faecium in milk-based systems.

Untreated whole milk, skim milk, sweetened milks, sweetened and unsweetened creams and ice-cream mixes were preincubated with a culture of Enterococcus faecium, then subjected to heat treatment in a pilot-scale plate heat exchanger using a hold of 15 s at 76 degrees C. The liquids were examined for gamma-glutamyltranspeptidase (GGTP) activity and total streptococcal count before and after heat treatment and the results plotted against water activity (aW). There was a good correlation between reduction in GGTP activity, destruction of streptococci and aW, demonstrating the potential of the enzymic assay for assessing the severity of HTST heat treatments above the minimum for pasteurization.

Tumor Necrosis Factor-Mediated Effects on Gamma-Glutamyl Transpeptidase Activity in Cloned Cerebral Endothelial Cells

Gamma-glutamyl transpeptidase (γ-GTP), a marker enzyme for blood brain barrier (BBB) function, was induced consistently by TNF (500 U/mL) in cerebral endothelial cells (cEC) compared with control cultures. The enzyme activity was found to be considerably lower in pulmonary artery cells, where, when treated with TNF (500 U/mL), the induction was not observed. Pre-incubation with zinc (1 μg/mL)-enriched media for 48 hours did not block TNF-mediated activation of γ-GTP. The increase in γ-GTP activity does not appear to be mediated through the cAMP signal transduction pathway as evidenced by the lack of TNF-mediated intracellular accumulation of cAMP. In addition, forskolin failed to influence γ-GTP enzyme activity, which further suggests that cAMP is not involved. Phospholipase A2, an enzyme involved in the arachidonic acid pathway, appears to be implicated in TNF signalling across the membrane of cEC. Two inhibitors of phospholipase A2, mepacrine and p-bromophenacyl-bromide (BPB), depressed the activity of ...

Topochemistry of Membrane Proteases in Vessels of Guinea Pig Subfornical Organ.

Localization of membrane-bound proteases, glutamyl aminopeptidase (EAP), microsomal alanyl aminopeptidase (mAAP), dipeptidyl peptidase IV (DPP-IV), and γ-glutamyl transpeptidase (γ-GTP), which may participate in the metabolism of various peptides, was studied in guinea pig subfornical organ (SFO). The reaction products of these enzymes were localized in both small vessels located in the central part of SFO and large vessels present in the peripheral part of SFO. The small vessels showed positive enzyme activity for mAAP and γ-GTP, traces for EAP, but a negative reaction for DPP-IV. The large vessels showed positivity in various intensities for mAAP, EAP, and DPP-IV; however, γ-GTP enzyme activity was not present. In the ependyma which cover the SFO, the enzyme-histochemical reactions for mAAP, EAP and DPP-IV were negative, and γ-GTP activity was not clearly demonstrated. In vessels of the choroid plexus in the vicinity of SFO, the reactions for mAAP and EAP were positive, but negative for DPP-IV and γ-GTP. Epithelium of this part of the choroid plexus was positive for γ-GTP but negative for mAAP, EPA, and DPP-IV. Differences in the location and enzyme activity of mAAP, EAP, DPP-IV, and γ-GTP in different vascular compartments, ie., differences among small and large vessels of guinea pig SFO, and vessels of choroid plexus in the vicinity of the SFO, suggest different roles for vascular endothelium in influencing the blood-borne peptides which would be dependent on the spectrum of membrane-bound peptidases present on cells in these structures.

The relationship of astrocyte-like cells to the vessels that contribute to the blood-ocular barriers

Brain capillaries form a selective interface, the blood-brain barrier (BBB), between the neural parenchyma and the blood. The factors which regulate this interface are poorly understood. Both the iris and retina possess vascular beds that express some BBB characteristics; therefore, they provide attractive models to further our understanding of how blood-tissue interfaces are regulated. We have determined whether three BBB markers: the transferrin receptor, P-glycoprotein, and gamma-glutamyl transpeptidase (γ-GTP), can be localized in the capillaries of the rat retina and iris. We have also compared, in retina and iris, the relationship which GFAP-positive cells have with the blood vessels to the expression of the three BBB markers by the vessels. Immunocytochemistry revealed that capillaries throughout the retina express P-glycoprotein and the transferrin receptor. Retinal vessels do not show detectable γ-GTP activity. GFAP-positive cells ensheath capillaries in the nerve fibre layer of the retina. Of the three BBB characteristics we examined, iridial vessels expressed only one of them; P-glycoprotein. In the iris, GFAP-positive cells do not ensheath capillaries. From our results we conclude that all BBB characteristics do not have to be expressed and regulated in capillaries as a unit. Our results, in combination with those of earlier studies, suggest that the expression of some BBB features does not require intimate contact between capillaries and astrocytes or astrocyte-like cells. Barrier maintenance appears to be a complex process which involves the integration of several factors.

Glutathione Cycle Dependency of Ferric Nitrilotriacetate-Induced Lipid Peroxidation in Mouse Proximal Renal Tubules

Parenteral administration of ferric nitrilotriacetate (Fe-NTA), a known carcinogen in mouse and rat kidneys, enhances iron-dependent lipid peroxidation (LP) and causes acute renal tubular necrosis. We assume that filtered Fe-NTA in vivo is rapidly reduced by cysteine, a component of glutathione which is hydrolyzed by γ-GTP and dipeptidase, and that this reduced iron initiates lipid peroxidation in the lumen. In addition, the fatty acid composition of phospholipids between the cortex and the medulla may differ, because only the proximal tubules (which are located mainly in the cortex) are known to be vulnerable to LP. We tested these assumptions in the present study. Gas chromatographic determination of fatty acid composition in five male and five female 6-week-old normal ddY mice showed the ratio of polyunsaturated fatty acids to saturated fatty acids plus C18:1, a single double-bond fatty acid, to be 0.98 ± 0.08 (av ± SD) in the male cortex and 1.00 ± 0.08 in the female cortex. In the male and female medulla, however, it was 0.78 ± 0.09 (P > 0.05, vs cortex) and 0.68 ± 0.04 (P > 0.01, vs cortex), respectively. Pretreatment of the animals with buthionine sulfoximine, a glutathione synthetase inhibitor, and a procedure that reduces total glutathione content in the kidneys, suppressed LP. Reduced thiobarbituric acid reactive substances were also observed in animals treated with AT-125, a γ-GTP inhibitor, and in animals with immature γ-GTP activity. These results are consistent with our assumptions.

Serum .GAMMA.-Glutamyl Transpeptidase Level and Daily Physical Activity.

Drinking habits and health are very important topics (Imura .et al., 1988; Morimoto et al., 1988). Bando et al. (1988) reported the results of a series of investigations conducted on this subject at the Japanese Association of Rural Medicine. They stated that serum γ-glutamyl transpeptidase (γ-GTP) activity is one of the most useful biochemical indices for an objective evaluation of the consumption of alcoholic beverages (Rosalki and Rau, 1972). On the other hand, there is rapidly rising interest in athletic activities such as jogging and the marathon. It is believed to be worthwhile in the field of sports medicine as well as for daily health management to establish the range of variation of serum γ-GTP activity levels in healthy individuals who engage in these athletic activities. Studies have been conducted on the relationship between physical activities and serum enzyme activity. However most of these studies were conducted on male adults, and female adults were rarely selected as subjects. Furthermore the subjects in many studies were athletes who engaged in intense physical activity and the data were obtained before and after the athletic activity (Krauss et al., 1977; Lewis et al., 1976). In this study, three types of tests were conducted to evaluate the relationship between serum γ-GTP level and physical activity; survey on energy expenditure, a shortterm exercise test, and a 6-week exercise program.