Decrease In Arginase Activity Research Articles

Maternal Immune Response to ZIKV Triggers High-Inflammatory Profile in Congenital Zika Syndrome.

The immunological mechanisms involved in the development of congenital Zika syndrome (CZS) have yet to be fully clarified. This study aims to assess the immuno-inflammatory profile of mothers and their children who have been diagnosed with CZS. Blood samples, which were confirmed clinically using the plaque reduction neutralization test (PRNT), were collected from children with CZS and their mothers (CZS+ group). Samples were also collected from children who did not develop CZS and had a negative PRNT result and from their mothers (CZS- group). The data demonstrated a correlation between the leukocyte profile of CZS+ children and their mothers, more evident in monocytes. Monocytes from mothers of CZS+ children showed low expression of HLA and elevated hydrogen peroxide production. CZS+ children presented standard HLA expression and a higher hydrogen peroxide concentration than CZS- children. Monocyte superoxide dismutase activity remained functional. Moreover, when assessing the monocyte polarization, it was observed that there was no difference in nitrite concentrations; however, there was a decrease in arginase activity in CZS+ children. These data suggest that ZIKV infection induces a maternal immuno-inflammatory background related to the child's inflammatory response after birth, possibly affecting the development and progression of congenital Zika syndrome.

CHANGES IN THE ACTIVITY OF INDUCIBLE NO-SYNTHASE AND ARGINASE, THEIR RELATIONSHIP WITH THE LEVEL OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN CERVICAL MUCUS IN PREGNANT WOMEN, WHO UNDERWENT IVF AND ARE AT RISK OF PRETERM CHILDBIRTH

Introduction. Nitric oxide (NO) produces a wide range of bioregulatory effects. Imbalance in the ratio of the activity of inducible NO-synthase and arginase in favor of iNOS can lead to a pro-inflammatory reaction. At the risk of preterm childbirth, the content of proinflammatory cytokines increases both at the local and systemic levels. The aim of this work is to study the relationship between changes in the content of pro- and anti-inflammatory cytokines and the activity of inducible NO-synthase and arginase in the cervical mucus of women with in vitro fertilization (IVF), who are at risk of preterm childbirth. Materials and methods. The test group (TG) included 37 women, who underwent IVF and presented prognostic signs, indicating a high risk of preterm birth in the future. The control group (CP) consisted of 20 healthy pregnant women, who did not undergo assisted reproductive technologies. We determined the indicators of inducible NO-synthase activity and total arginase activity, as well as the level of pro- and anti-inflammatory cytokines in the mucus of the cervical canal of the participants at their 28-34 weeks of pregnancy. Results and discussion. The activity of iNOS in TG significantly increased (in 2.57 times) compared to healthy pregnant women (CP), while the activity of arginase, on the contrary, decreased significantly (in 1.91 times). There was a significant increase in the levels of pro-inflammatory cytokines INF-γ and TNF-α in the TG women, while they demonstrated the significantly reduced concentration of anti-inflammatory cytokine IL-10. In cervical mucus taken from TG women, positive correlations were found between an increase in the concentration of the proinflammatory cytokine INF-γ and an increase in iNOS activity, between a decrease in IL-10 levels and arginase activity, and a negative relationship between an increase in iNOS activity and a decrease in arginase activity. Conclusions. The detected cytokine imbalance in pregnant women, who underwent in vitro fertilization and were at risk of preterm childbirth, together with a impaired ratio of iNOS and arginase, indicates an inappropriate level of immunosuppression. These immune changes, by activating cellular responses of maternal immunity, can contribute to preterme childbirth.

PDE-5 Inhibition Decreases Cancer Tumor Burden through Immunomodulation

Myeloid-derived suppressor cells (MDSC) are CD14-/CD11b+/Gr1+ cells that have been shown to suppress T-cell anti-tumor activity. They do so namely by using arginase and iNOS to deplete the microenvironment of L-arginine and producing unopposed NO, respectively. Sildenafil, a PDE5 inhibitor, has been shown to decrease tumor burden and increase T-cell tumor infiltration, though its mechanism is poorly understood. This study aimed at determining the mechanisms by which Sildenafil affected MDSC suppression mechanisms on cytotoxic T-cells and investigate the effects on invasive 4T1 cancer cells both in vitro and in vivo.In our in vitro model, lymphoid cells were obtained from 4T1 tumor bearing BalbC mice 14 days after exposure and extracted using a magnetic bead separation technique, then expanded for 6 days using ionomicin, bryostatin and IL-2 pulsed for 24 hours followed by IL-7 and IL-15 in RPMI and FBS media. MDSCs were obtained from the spleens of 4T1 exposed mice. The sildenafil-exposed MDSCs showed a significant decrease in arginase activity. Additionally, when cultured in sildenafil and media, 4T1 cells showed a 50% reduction in growth. In this same model, T-cells had a 13% increase in growth with a therapeutic dose of sildenafil.In vivo studies were performed using BalbC mice injected with 4T1 cells and treated with sildenafil injections as well as PBS control injections. Spleens were harvested at day 14 and purified using flow cytometry to GR1 and CD11b antigens. Sildenafil-treated mice showed a 43% decrease in tumor burden and a significant decrease in arginase activity, though iNOS levels showed no significant difference between groups. The MDSC pathway remains a promising area of study in allowing activated T-cells to decrease tumor and the use of sildenafil has proven effective in reducing MDSC activity through decreases in arginase activity. DisclosuresNo relevant conflicts of interest to declare.

ARGININE/CITRULLINE CYCLE CHANGES IN DIET-INDUCED RAT MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE

The aim: to study the Arginine / Citrulline-cycle features on a diet-induced rat model of non-alcoholic fatty liver disease (NAFLD). Materials and methods: The studies were carried out on 20 white non-linear adult rats, including 10 (50%) males, 10 (50%) females, weighing 160-220 g. NAFLD was modeled by a 9-week fast food diet. The level of arginine and citrulline, and the arginase activity were investigated in the animals' liver homogenates and in the blood. The morphological analysis of liver tissues changes was done. Results: NAFLD modeling using a 9-week fast food diet resulted in maximum weight gain in male rats (р<0.05). Female rats had 3 times more accumulation of intra-abdominal fat than male rats in the main group (р<0.05). Histopathologic liver examination confirmed NAFLD development in rats on a fast food diet during 9 weeks (р<0.05). NAFLD led to an increment of arginine level in the blood and liver homogenate in the main group compared to controls (р<0.05). NAFLD development was accompanied by a decrease in arginase activity and citrulline level in the blood and liver homogenate compared to control (р<0.05). Conclusions: The experimental rat model of NAFLD showed the Arginine / Citrulline cycle disorders, that were characterized by an increased arginine level, a decreased arginase activity and citrulline concentration in the blood and liver tissues.

The Effect of Ramadan Fasting on Arginase Activity in Healthy Volunteers

The practice of fasting is performed by many communities for religious or spiritual reasons. Additionally, in the recent years many health benefits were associated with different kinds of fasting. These include: controlling blood glucose levels , reducing insulin resistance, reducing inflammation, improve heart health, lowering blood pressure and boosting brain function while prevent neurodegenerative disorders. Moreover, there is proven evidence on the effects of Ramadan fasting, performed by muslims for one month, on improving vascular health, blood flow and enhancing endothelial function in patients with cardiovascular disease. Fasting was reported to increase nitric oxide (NO) levels and decrease asymmetric dimethylarginine (ADMA); a novel cardiovascular risk factor. Nitric oxide, a potent vasodilator and vascular protective molecule, is produced by endothelial cells by the action of endothelial nitric oxide synthase (eNOS) on L‐arginine. Arginase, an enzyme implicated in many cardiovascular diseases, can compete with eNOS for their common substrate, L‐arginine to produce urea and ornithine. We and others have reported the effects of arginase inhibition on improving endothelial function and NO levels in different cardiovascular diseases and in diabetes.Our project aims to study the effect of Ramadan fasting on arginase activity in healthy individuals. We measured arginase activity one day before the start of fasting and on the last day of fasting for thirteen young male adults, ages between 18–35 years old. The fasting performed is to withhold from eating, drinking and smoking from sunrise to sunset (about 15 hours) everyday for a period of one month. Plasma arginase activity is measured using a colorimetric reaction of urea production. Our results show a modest though significant decrease in arginase activity of 15.7 ± 4.2%. We also determined basal urea levels and observed no change in these levels. Our results propose one important benefit of fasting through lowering arginase activity thus reserving available L‐arginine for NOS and increasing NO levels. We also noted that basal urea levels did not change. It was expected that not drinking water for long hours could increase chances of dehydration which can increase plasma urea concentrations, but this did not occur. In conclusion, our result show another added health benefit of fasting to the vascular system which is lowering arginase activity. Fasting under doctor supervision can be used in selected patients with vascular diseases to maintain and promote NO levels. We yet have to determine the effects of fasting on other systems of the body such as liver and kidney to preclude any deleterious side effects of this practice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats.

Exposure to either lead (Pb) or γ-irradiation (IR) results in oxidative stress in biological systems. Herein, we explored the potential anti-apoptotic effect of spermine (Spm) against lead and/or γ-irradiation-induced hepatotoxicity in male albino rats. Rats were divided into eight experimental groups of ten rats each: groups including negative control, whole body γ-irradiated (6Gray (Gy)), lead acetate (PbAct) trihydrate orally administered (75mg/kg bw≡40mg/kg bw Pb for 14 consecutive days), and Spm intraperitoneally dosed (10mg/kg bw for 14 consecutive days) rats and groups subjected to combinations of Pb+IR, Spm+IR, Spm+Pb, and Spm+Pb followed by IR on day 14 (Spm+Pb+IR). A significant decrease in arginase activity as well as mRNA and protein levels of Bcl-2 and p21 was observed in rats intoxicated with Pb and/or γ-irradiation compared to controls, whereas Bax mRNA and protein levels were significantly increased. Also, an increased level of nitric oxide (NO) with a reduced arginase activity was observed in liver tissues of intoxicated rats. Spm co-treatment with lead and/or γ-irradiation attenuated the increase in Bax mRNA and protein expression, while it restored those of Bcl-2 and p21 together with NO levels and arginase activity to control values. Altogether, we suggest that Spm may be useful in combating free radical-induced apoptosis in Pb-intoxicated and/or γ-irradiated rats.

Nitric Oxide-Related Biological Pathways in Patients with Major Depression.

BackgroundMajor depression is a well-known risk factor for cardiovascular diseases and increased mortality following myocardial infarction. However, biomarkers of depression and increased cardiovascular risk are still missing. The aim of this prospective study was to evaluate, whether nitric-oxide (NO) related factors for endothelial dysfunction, such as global arginine bioavailability, arginase activity, L-arginine/ADMA ratio and the arginine metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) might be biomarkers for depression-induced cardiovascular risk.MethodsIn 71 in-patients with major depression and 48 healthy controls the Global Arginine Bioavailability Ratio (GABR), arginase activity (arginine/ornithine ratio), the L-arginine/ADMA ratio, ADMA, and SDMA were determined by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at baseline at the time of in-patient admittance and at the time of hospital discharge.ResultsThe ADMA concentrations in patients with major depression were significantly elevated and the SDMA concentrations were significantly decreased in comparison with the healthy controls. Even after a first improvement of depression, ADMA and SDMA levels remained nearly unchanged. In addition, after a first improvement of depression at the time of hospital discharge, a significant decrease in arginase activity, an increased L-arginine/ADMA ratio and a trend for increased global arginine bioavailability were observed.ConclusionsOur study results are evidence that in patients with major depression ADMA and SDMA might be biomarkers to indicate an increased cardiovascular threat due to depression-triggered NO reduction. GABR, the L-arginine/ADMA ratio and arginase activity might be indicators of therapy success and increased NO production after remission.

Interferon-Gamma-Induced Nitric Oxide Inhibits the Proliferation of Murine Renal Cell Carcinoma Cells

Renal cell carcinoma (RCC) remains one of the most resistant tumors to systemic chemotherapy, radiotherapy, and immunotherapy. Despite great progress in understanding the basic biology of RCC, the rate of responses in animal models and clinical trials using interferons (IFNs) has not improved significantly. It is likely that the lack of responses can be due to the tumor's ability to develop tumor escape strategies. Currently, the use of targeted therapies has improved the clinical outcomes of patients with RCC and is associated with an increase of Th1-cytokine responses (IFNγ), indicating the importance of IFNγ in inhibiting tumor proliferation. Thus, the present study was designed to investigate a new mechanism by which IFNγ mediates direct anti-proliferative effects against murine renal cell carcinoma cell lines. When cultured RCC cell lines were exposed to murine recombinant IFNγ, a dose dependent growth inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with the intracellular induction of nitric oxide synthase (iNOS) protein, resulting in a sustained elevation of nitric oxide (NO) and citrulline, and a decrease in arginase activity. The inhibition of cell proliferation appears to be due to an arrest in the cell cycle. The results indicate that in certain RCC cell lines, IFNγ modulates L-arginine metabolism by shifting from arginase to iNOS activity, thereby developing a potent inhibitory mechanism to encumber tumor cell proliferation and survival. Elucidating the cellular events triggered by IFNγ in murine RCC cell lines will permit anti-tumor effects to be exploited in the development of new combination therapies that interfere with L-arginine metabolism to effectively combat RCC in patients.

Arginase isoenzymes in human cirrhotic liver.

Cirrhosis leads to an inability of the liver to perform its biochemical functions. It can also lead to hepatocellular carcinoma in which, as we showed lately, arginase isoenzyme pattern changes. The present work presents our results on arginase isoenzymes and their possible role in liver cirrhosis. The study was performed on tissues obtained during liver transplantation from 60 patients with liver cirrhosis, and on samples of histologically normal liver (control) from 40 patients with benign or colorectal cancer liver metastases removed during surgery, 6-7 cm from the tumor border. Arginase isoenzymes AI (so-called liver-type arginase) and AII (called extrahepatic arginase) were identified by Western blotting and isolated by ion-exchange chromatography. Their expression on mRNA level was studied by RT-PCR. A significant decrease in arginase activity, dependent of the liver clinical stage, was observed in cirrhotic tissue. Arginase AI activity and its mRNA level were significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII were concurrently raised, as compared to normal liver. Since arginase AI is a key enzyme of the urea cycle, whereas arginase AII most probably takes part in the biosynthesis of ornithine and polyamines, the defective ammonia inactivation and increased collagen biosynthesis observed in cirrhotic liver may be related to the changes in arginase AI and AII levels, respectively.

Effect of psychological stress on the L-arginine-nitric oxide pathway and semen quality

It has been reported that mental stress causes abnormality of spermiogram parameters. We investigated the effect of psychological stress on the L-arginine-nitric oxide (NO) pathway. Semen samples were collected from 29 healthy fourth semester medical students just before (stress) and 3 months after (non-stress) the final examinations. Psychological stress was measured by the State Anxiety Inventory questionnaire. After standard semen analysis, arginase activity and NO concentration were measured spectrophotometrically in the seminal plasma. Measurements were made in duplicate. During the stress period, sperm concentration (41.28 +/- 3.70 vs 77.62 +/- 7.13 x 10(6)/mL), rapid progressive motility of spermatozoa (8.79 +/- 1.66 vs 20.86 +/- 1.63%) and seminal plasma arginase activity (0.12 +/- 0.01 vs 0.22 +/- 0.01 U/mL) were significantly lower than in the non-stress situation, whereas seminal plasma NO (17.28 +/- 0.56 vs 10.02 +/- 0.49 micromol/L) was higher compared to the non-stress period (P < 0.001 for all). During stress there was a negative correlation between NO concentration and sperm concentration, the percentage of rapid progressive motility and arginase activity (r = -0.622, P < 0.01; r = -0.425, P < 0.05 and r = -0.445, P < 0.05, respectively). These results indicate that psychological stress causes an increase of NO level and a decrease of arginase activity in the L-arginine-NO pathway. Furthermore, poor sperm quality may be due to excessive production of NO under psychological stress. In the light of these results, we suggest that the arginine-NO pathway, together with arginase and NO synthase, are involved in semen quality under stress conditions.

In hepatocytes the regulation of NOS-2 activity at physiological l-arginine levels suggests a close link to the urea cycle

High-output synthesis of nitric oxide (NO) by the inducible isoform of NO-synthases (NOS-2) plays an important role in hepatic pathophysiological processes and may contribute to both organ protection and organ destruction during inflammatory reactions. As they compete for the same substrate, L-arginine, an interdependence of NOS-2 and arginase-1 has been repeatedly observed in cells where arginase-1 is cytokine-inducible. However, in hepatocytes, arginases are constitutively expressed and thus, their impact on hepatic NOS-2-derived NO synthesis as well as the influence of L-arginine influx via cationic amino acid transporters during inflammatory reactions are still under debate. Freshly isolated rat hepatocytes were cultured for 24h in the presence of various L-arginine concentrations with or without cytokine addition and nitrite and urea accumulation in culture supernatants was measured. We find that both, cytokine-induced NOS-2 and arginase activities strongly depend on extracellular L-arginine concentrations. When we competed for L-arginine influx via the cationic amino acid transporters by addition of L-lysine, we find a 60-70% inhibition of arginase activity without significant loss of NOS-2 activity. Addition of L-valine, as an arginase inhibitor, leads to a 25% increase in NO formation and an 80-90% decrease in arginase activity. Interestingly, product inhibition of arginase and competitive inhibition of CATs through the addition of L-ornithine leads to a highly significant increase in hepatocytic NOS-2 activity with a concomitant and complete abolishment of its dependence on extracellular L-arginine concentrations. In conclusion, hepatocytic NOS-2 activity shows a surprising pattern of dependence on exogenous L-arginine concentrations. Inhibition and competition experiments suggest a relatively tight link of NOS-2 and urea cycle activities. These data stress the hypothesis of a metabolon-like organization of the urea cycle together with NOS-2 in hepatocytes as excess L-ornithine will be metabolized to l-arginine and thereby increases NO production.

The effect of melatonin treatment on oxidative and nitrosative stress in rats with thioacetamide-induced hepatic damage

: The following study aimed to clarify the importance of arginase and NOS activities in thioacetamide-induced hepatic damage and to evaluate the underlying mechanism of proposed protection provided by melatonin, using commonly applied therapeutic dose. : Rats were randomly assigned to four groups (n=5): control, melatonin (10mg/kg i.p.), thioacetamide (200mg/kg i.p., two doses with a 24h interval) and thioacetamide+three doses of melatonin (10mg/kg i.p., prior- and post-treatment with a 24h interval before thioacetamide administrations) treated groups. : Thioacetamide administration caused hepatic damage creating oxidative and nitrosative stress accompanying perivenous necrosis and eosinophil infiltration. The significant elevation of total nitrite level in livers of thioacetamide treated groups reflected the activation of inducible nitric oxide synthase activity. The decrease in arginase activity indicated hepatic damage. Non-altered specific activity of arginase in the livers of thioacetamide treated groups did not overcome the elevation of NO production. Melatonin treatment did not modulate the levels/activities significantly. : Our results have indicated that nitrosative stress seems to be essentially critical in thioacetamide-induced hepatic failure in rats. Possible regulatory effect of arginase on NO production and applied dose of melatonin could not prevent hepatic damage.

Evaluation of optimal conditions for arginase activity in streptozotocin induced diabetic rats

The assay conditions needed to achieve maximal activity of liver and kidney arginase in diabetic and non-diabetic rats were investigated and compared. The physicochemical and kinetic properties of liver arginase in diabetic and control rats were very similar, those of kidney arginase were significantly different. It was found that preincubation temperature (68&amp;deg;C), preincubation period (20 min), optimum pH (10.1) of liver arginase and K&lt;sub&gt;m&lt;/sub&gt; (3.2) for its substrate, L-arginine, did not change in diabetic and non-diabetic rats. As a consequence of diabetes, the optimum Mn&lt;sup&gt;2+&lt;/sup&gt; concentration for liver arginase only changed from 1 to 2 mM. Although the preincubation temperature and period for activation of kidney arginase in control rats was unnecessary, they were found to be 56&amp;ordm;C and 12 min in diabetic rats. The pH profile of arginase in kidney of diabetic rats was different from that of control rats. The K&lt;sub&gt;m&lt;/sub&gt; value (6.7) of arginase for L-arginine in kidney is unchanged in diabetes whereas a marked decrease in V&lt;sub&gt;max&lt;/sub&gt; was found. Optimum Mn&lt;sup&gt;2+&lt;/sup&gt; concentration (2 mM) for kidney arginase was unchanged in diabetes. The activity of arginase in liver of diabetic animals was higher 1.5 to 1.7 times than that of controls. Diabetes caused an about 53% decrease of arginase activity in kidney of female rats, 26% in that of males. These findings may suggest an idea that encoded arginases by separate gene loci may be affected differently by the pathological and hormonal status.

Sex steroid hormones differentially regulate nitric oxide synthase and arginase activities in the proximal and distal rabbit vagina.

Nitric oxide synthase (NOS) and arginase have been shown to regulate nitric oxide (NO) production reciprocally in genital tissues. In animal models, NO is an important regulator of vaginal blood flow and vaginal wall contractility. In this study, we investigated the modulation of NOS and arginase activities by estrogens and androgens in the proximal and distal rabbit vagina. In intact control animals, total NOS activity was higher in the proximal (528+/-78 pmol/mg protein) than the distal (391+/-44 pmol/mg protein) vagina. However, arginase activity was higher in the distal (206+/-8 nmol/mg protein) than the proximal (64+/-5 nmol/mg protein) vagina. Ovariectomy enhanced NOS activity in the proximal but not distal vagina with concomitant decrease in arginase activity in both the proximal and distal vagina. In ovariectomized rabbits, replacement with 5alpha-dihydrotestosterone (DHT) or Delta5-androstenediol (Adiol) increased NOS activity beyond that observed in ovariectomized rabbits receiving vehicle. In contrast, DHT and Adiol treatment reduced arginase activity more than that of the ovariectomized rabbits receiving vehicle. Testosterone exhibited inconsistent effects on NOS and arginase activity in the distal and proximal vagina. Estradiol replacement in ovariectomized animals reduced NOS activity in the proximal vagina down to levels that were comparable to intact control animals. However, estradiol positively modulated arginase activity in the distal vagina. Western blot analyses indicated that in the proximal vagina, neural NOS protein levels paralleled the changes observed in enzyme activity. These observations suggest that steroid hormones differentially regulate NOS and arginase activities of the proximal and distal regions of the vagina. Although estrogen treatment reduced total NOS activity in proximal vagina, estrogens are known to enhance vaginal blood flow. This paradoxical observation may be explained by differential regulation of n-NOS and e-NOS in the proximal and distal vagina. We suggest that changes in vaginal blood flow and compliance may depend on the endocrine status and the levels of circulating androgens and estrogens.

RIFN-γ-mediated growth suppression of platinum-sensitive and -resistant ovarian tumor cell lines not dependent upon arginase inhibition

BackgroundArginine metabolism in tumor cell lines can be influenced by various cytokines, including recombinant human interferon-γ (rIFN-γ), a cytokine that shows promising clinical activity in epithelial ovarian cancer (EOC).MethodsWe examined EOC cell lines for the expression of arginase in an enzymatic assay and for transcripts of arginase I and II, inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO) by reverse transcription-polymerase chain reaction. The effects of rIFN-γ on arginase activity and on tumor cell growth inhibition were determined by measuring [3H]thymidine uptake.ResultsElevated arginase activity was detected in 5 of 8 tumor cell lines, and analysis at the transcriptional level showed that arginase II was involved but arginase I was not. rIFN-γ reduced arginase activity in 3 EOC cell lines but increased activity in the 2008 cell line and its platinum-resistant subline, 2008.C13. iNOS transcripts were not detected in rIFN-γ-treated or untreated cell lines. In contrast, IDO activity was induced or increased by rIFN-γ. Suppression of arginase activity by rIFN-γ in certain cell lines suggested that such inhibition might contribute to its antiproliferative effects. However, supplementation of the medium with polyamine pathway products did not interfere with the growth-inhibitory effects of rIFN-γ EOC cells.ConclusionsIncreased arginase activity, specifically identified with arginase II, is present in most of the tested EOC cell lines. rIFN-γ inhibits or stimulates arginase activity in certain EOC cell lines, though the decrease in arginase activity does not appear to be associated with the in vitro antiproliferative activity of rIFN-γ. Since cells within the stroma of EOC tissues could also contribute to arginine metabolism following treatment with rIFN-γ or rIFN-γ-inducers, it would be helpful to examine these effects in vivo.

Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: regional variations and age-related changes.

Increasing evidence suggests that nitric oxide synthase (NOS)/nitric oxide (NO) contributes to the aging process. By contrast, the role of arginase, which shares a common substrate with NOS, has not been determined. In the present study, regional variations and age-related changes in NOS and arginase in the hippocampus and its neighboring structures were investigated for the first time. In young adult rats, high levels of NOS activity were found in the entorhinal, perirhinal, and postrhinal cortices, whereas low values were located in the hippocampus and the temporal cortex. Interestingly, arginase activity showed an overall inverse pattern with the lowest levels in the entorhinal and perirhinal cortices. When a comparison was carried out between young (4-month-old) and aged (24-month-old) rats, significant increases in total NOS activity were found in the aged entorhinal and temporal cortices, and a significant decrease in arginase activity was observed in the aged postrhinal cortex. Western blotting demonstrated significant decreases in both neuronal and endothelial NOS expression in the aged hippocampus and postrhinal cortex, whereas arginase I and II expression did not show age-related changes in any region examined. Activity and protein expression of inducible NOS were not detected in any tissue from either group. The present findings of region-specific changes in NOS and arginase appear to support the potential involvement of NOS/NO in the aging process and raise the issue of a possible contribution of arginase to aging.

Arginase, Arginine Decarboxylase, Ornithine Decarboxylase, and Polyamines in Tomato Ovaries (Changes in Unpollinated Ovaries and Parthenocarpic Fruits Induced by Auxin or Gibberellin).

Arginase (EC 3.5.3.1) activity has been found in the ovaries and Young fruits of tomato (Lycopersicon esculentum Mill. cv Rutgers).Changes in arginase, arginine decarboxylase (EC 4.1.1.19), and ornithine decarboxylase activity (EC 4.1.1.17) and levels of free and conjugated putrescine, spermidine, and spermine were determined in unpollinated ovaries and in parthenocarpic fruits during the early stages of development induced by 2,4-dichlorophenoxyacetic acid (2,4-D) or gibberellic acid (GA3). Levels of arginase, free spermine, and conjugates of the three polyamines were constant in unpollinated ovaries and characteristic of a presenescent step. A marked decrease in arginase activity, free spermine, and polyamine conjugates was associated with the initiation of fruit growth due to cell division, and when cell expansion was initiated, the absence of arginase indicated a redirection of nitrogen metabolism to the synthesis of arginine. A transient increase in arginine decarboxylase and ornithine decarboxylase was also observed in 2,4-D-induced fruits. In general, 2,4-D treatments produced faster changes than GA3, and without treatment, unpollinated ovaries developed only slightly and senescence was hardly visible. Sensitivity to 2,4-D and GA3 treatment remained for at least 2 weeks postanthesis.

AN ARGINASE INHIBITOR(S) AND ITS POSSIBLE ROLE IN THE DEVELOPMENTAL DECREASE OF ARGINASE ACTIVITY IN CHICK EMBRYOS

1. Arginase activity was measured in tissues of developing eggs from the first to the seventh day of incubation. Activity per unit moist weight or dry weight decreased in embryo, pellucida, vasculosa and vitellina.2. Evidence was obtained that all chick tissues studied contain a high molecular weight arginase inhibitor(s) which appears to be ribonucleic acid in nature.3. Inhibitor(s) seems to play a major role in establishing the level of arginase activity expressed by crude homogenates.4. The decreased arginase activity of hearts from developing embryos has been correlated with an increase in inhibitor activity.5. These results suggest that the developmental decrease in arginase activity could be the result of an increase in inhibitor concentration as well as of a decrease in enzyme concentration.