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Glutathione is a tri-peptide that plays key roles in antioxidation and detoxification. At present, research on glutathione metabolism mainly focuses on anabolism. And little is known about its catabolismin the cytoplasm. With the discovery of glutathione-specific γ-glutamylcyclotransferase ChaC1, thecatabolism of glutathione in the cytoplasm has gradually been unveiled. ChaC1 is one member of the γ-glutamylcyclotransferase (GGCT) family, catalyzing the degradation of glutathione and production of Cys-Gly and 5-oxoproline. ChaC1 is highly conserved, with a ~ 88% identity between human and mousegenes. Mutation of E115 in human ChaC1 or E116 in mouse ChaC1 abolishes its enzymatic activity. Notably, ChaC1 deficiency leads to embryonic lethality in the mouse and zebrafish, indicating ChaC1 isessential for embryo development. On the other side, ChaC1 is highly expressed in different types ofcancer and correlates with a poor prognosis, suggesting that ChaC1 also has important pathophysiologicalfunction. In this paper, we review the research progress on the structure, enzymatic activity andexpression pattern of ChaC1 in recent years, and summarize the role of ChaC1 in development anddiseases, providing new insights on the mechanisms and therapeutic strategies.
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Objective To investigate the pretreatment and post-treatment effect of reduced glutathione (GSH) on acute ischemia-reperfusion injury (IRI) of rat kidney. Methods Fifty adult SD rats were divided into 5 groups: control group (Sham group), ischemia reperfusion group (I/R group), GSH pretreatment group (pre-treatment group), and GSH post-processing group (post-treatment group), with ten rates in each group. Animals in pre-treatment group were injected 4% GSH 100 mg/kg intraperitoneally at 24th , 16th , 8th hour and 45th minute before surgery. Animals in post-treatment group were administrated GSH with the same dosage at 45th minute, 6th, 12th and 18th hour after surgery. Creatinine (Cr), urea nitrogen (BUN) level, the total superox-ide dismutase (T-SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels in serum were measured at 24th hour after surgery. Histopathological changes were checked by H. E staining. Results Damage on kid-ney structure of animals in pre-treatment group was less than that in I/R group. There was little pathological change on kidney of those in pre-treatment group. Serum Cr, BUN, MDA and NO levels were all decreased but T-SOD activity increased in pre-treatment and post-treatment group when compared with those in I/R group (P <0.05), (P < 0.05). T - SOD activity in post-treatment group was higher than that in pre-treatment group (P <0.05). Conclusion GSH can protect rats against acute renal ischemia-reperfusion injury within 24 hours before and after kidney ischemia-reperfusion , especially after ischemia-reperfusion.
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Coal combustion generates considerable amount of ultrafine particles and exposure to such particulate matter is a major health concern in the developing countries. In this study, we collected nano sized coal fly ash (CFA) and characterized them by scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), particle size analyzer (PSA) and transmission electron microscope (TEM), and investigated its toxicity in vitro using different cell lines. The imaging techniques showed that the coal fly ash nanoparticles (CFA-NPs) are predominately spherical shaped. The analyses have revealed that the CFA-NPs are 7-50 nm in diameter and contain several heavy metals associated with CFA particles. The studies showed significant amount of toxicity in all cell lines on treatment with CFA-NPs. The cytotoxicity and oxidative DNA damage caused by CFA-NPs were determined by inhibition of cellular metabolism (MTT), total intracellular glutathione (GSH), reactive oxygen species (ROS) and DNA fragmentation in cultured cell lines (Chang liver, HS294T and LL29). The cellular metabolism was inhibited in a dose-dependent manner in CFA-NPs treated cell lines. The CFA-NPs induced ROS and decreased the total intracellular glutathione with increased dose. Further, the CFA-NPs treated cells showed severe DNA laddering as a result of DNA fragmentation.
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Background & objectives: Oxidative stress contributes to severity of ulcerative colitis (UC) but the status of erythrocyte antioxidant defence remains unknown. The present study was aimed to study the role of oxidative stress and antioxidant levels in erythrocytes of UC patients from north India. Methods: A total of 81 adult UC patients and 85 age and sex matched apparently healthy controls were included in this study. Levels of lipid peroxidation (LPO), reduced glutathione (GSH), catalase and superoxide dismutase (SOD) were measured in erythrocytes. Results: Mean age of UC patients was 43.5 yr (range 18-64 yr) while in the control group this was 45.3 yr (range 20-64 yr). LPO, catalase and SOD levels in UC patients were significantly increased (P<0.05) compared to healthy controls, while GSH levels in UC patients were significantly decreased (P<0.05) compared to healthy controls Ulcerative colitis activity score (UCAI) was 157.4±27.6 in UC patients. Interpretation & conclusions: Increased levels of LPO, SOD, catalase and a decreased level of GSH represent that oxidative stress plays a significant role in pathophysiology of UC. Further, the levels of LPO, GSH, catalase and SOD remained same during different UCAI.
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Glutathione (GSH) protects cells against oxidative stress by playing an antioxidant role. Protecting brain endothelial cells under oxidative stress is key to treating cerebrovascular diseases and neurodegenerative diseases including Alzheimer's disease and Huntington's disease. In present study, we investigated the protective effect of GSH on brain endothelial cells against hydrogen peroxide (H2O2). We showed that GSH attenuates H2O2-induced production of nitric oxide (NO), reactive oxygen species (ROS), and 8-Oxo-2'-deoxyguanosine (8-OHdG), an oxidized form of deoxiguanosine. GSH also prevents H2O2-induced reduction of tight junction proteins. Finally, GSH increases the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and activates Nrf2-mediated signaling pathways. Thus, GSH is a promising target to protect brain endothelial cells in conditions of brain injury and disease.
Subject(s)
Alzheimer Disease , Apoptosis , Brain Injuries , Brain , Endothelial Cells , Glutathione , Huntington Disease , Hydrogen Peroxide , Hydrogen , Neurodegenerative Diseases , Nitric Oxide , Oxidative Stress , Reactive Oxygen Species , Tight Junction ProteinsABSTRACT
The class of Actinobacteria is a large group of gram-positive bacteria and having high G+C content. Actinobacteria also produced curious compound like thiols mainly Mycothiol (MSH) and Glutathione (GSH). MSH is also known as mycothiol and comprised of a cysteine residue with an acetylated amino group which is linked to glucosamine to inositol but Glutathione (GSH) having gamma peptide linkage between cysteine group which is attached by normal peptide linkage to a glycine and the carboxyl group of the glutamate side-chain. These thiols play a key role in maintaining a reducing environment in the cell, which is necessary for regular metabolic activities and represent adaptation under stress condition for survival of organisms. Both Mycothiol and glutathione (GSH) having property to protect cells against oxygen toxicity but MSH shows 7 fold slower ability to resistance of autoxidation compare to GSH but GSH is absent in archaebacterium and rarely found in Streptomycetes strains (Streptomyces lactamdurans). In this review article we discussed about the GSH and MSH structure, properties and how GSH is better than MSH in the case of antioxidant production.
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The Angiotensin converting enzyme (ACE) is a dipeptidyl carboxypeptidase and plays an important role in the regulation of blood pressure. Several potent inhibitors of this enzyme have been reported to be active antihypertensive agents. Sulfhydryl (SH) group containing ACE inhibitors used as a antihypertensive agents. Reduced glutathione (GSH) as antioxidant play an important role in reducing the blood pressure. Several recent studies have shown that reduced glutathione enhance nitric oxide pathway and increases the bioavailability of nitric oxide resulting in vasodilatation. In this study reduced glutathione and oxidized glutathione (GS-SG) were investigated for inhibition against ACE using Hip-His-Leu (HHL) as substrate. The inhibition of ACE by different concentrations of reduced glutathione was much more than that of oxidized glutathione. The inhibition of ACE by reduced glutathione ranges from 12.5% to 60%. Oxidized glutathione shows less than 5% of inhibition. This study shows that apart from the antioxidant role, reduced glutathione inhibits ACE activity which plays a crucial role in the regulation of blood pressure.
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The objective of the present study was to investigate the effect of administration of 1 mM methylene blue (MB) in drinking water for 30 days on hepatic and renal antioxidant status in female adult Wistar strain rats (n=5). MB failed to induce significant change in any of the measured antioxidant defence parameters namely, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). However, a marginally significant (P<0.05) increase in the level of lipid peroxidation (LPx) was recorded in liver, while a reduction (P<0.05) in its level in the kidney was noticed. Serum alanine amino transferase (AlaAT) and creatinine levels significantly (P<0.001) decreased in MB treated rats without any change in blood urea nitrogen (BUN) level. Our findings suggest that the effect of MB as administered in the present study was tissue specific with regard to the level of LPx, however, in general, it does not impair liver and kidney functions as evidenced by serum parameters.
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@#ObjectiveTo observe the effect of reduced glutathione(GSH) on expression of malondialdehyde(MDA),glutathione peroxidase(GSH-PX) and superoxide dismutase(SOD) after focal cerebral infarction in rats.MethodsRat models of middle cerebral artery occlusion(MCAO) were estabilished with thread after 2-hour ischemia and 6-hour reperfusion.Rats were divided at random into three groups,i.e.,sham-operated,control and treatment group(with GSH 1200 mg/kg) respectively.After the rats model was performed,neurology deficit score,the size of brain infarct region and the change of brain tissue pathologic were evaluated.Contents of MDA and activity of SOD and GSH-PX were detected with spectrophotometer.ResultsCompared with the control group,GSH can ameliorate neurological deficit score and decrease infarct volume induced by MCAO.GSH may reduce contents of MDA and improve activity of SOD and GSH-PX in brain tissue.ConclusionGSH may reduce contents of MDA and improve activity of SOD and GSH-PX so as to enhance capability of eliminating oxygen free radical,and play a neuroprotective effect after cerebral focal ischemia reperfusion.
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Mitomycin C (MMC)is used in trabeculectomy to promote the intraocular pressure control, but at the same time it also seems to increase the risk of cataract. In this study, we investigated the mechanism by which MMC causes lens opacity.The whole lenses were extracted from fertilized eggs of 11~13 days and cultured in M199 media supplemented with fetal bovine serum (FBS)at 38 degrees C.Levels of Lipid peroxidation (LPO)and Glutathione (GSH)were measured 24 hours and 5 minutes after treatment with 1 mg/ml MMC for 5 minutes.Changes of lenses by MMC were examined by light microscopy, and the modification of lens proteins was analyzed by SDS-PAGE and size exclusion column. Lens opacity was induced by MMC treatment in concentration of 1 mg/ml for 5 min, and MMC treated lenses showed 3 times higher LPO level and 2 times lower GSH level than normal lenses.In ultrastructure of opaque lenses, many vacuole formations in cortical area near equatorial zone were found.In electrophoresis followed by silver staining and size exclusion column profile, high molecular weight formation of lens proteins by MMC treatment was mainly due to disulfide bond.Also, when we treated the lens with antioxidants, the extent of opacity was decreased. In this study, we demonstrated that lenses treated with MMC became opaque mainly due to oxidative stress resulting in HMW formation of lens proteins by disulfide formation as well as irreversible oxidation.
Subject(s)
Antioxidants , Cataract , Crystallins , Electrophoresis , Electrophoresis, Polyacrylamide Gel , Glutathione , Intraocular Pressure , Lipid Peroxidation , Microscopy , Mitomycin , Molecular Weight , Oxidative Stress , Silver Staining , Trabeculectomy , Vacuoles , ZygoteABSTRACT
Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of y-glutamylcysteine synthetase(GCS), y-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR; L1210VcR, or L12100s) sublines were measured. Expression and amplification of GCS, GGT, and GST-i7 genes were also observed in the parent L1210 and the drug-resistant L1210 sublines. The concentration of GSH was increased 5.34 fold in L12100s, 2.83 fold in L1210VcR, and 1.78 fo-d in L1210AdR, compared to L1210. The activities of GCS and GGT were -increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to L1210. Expression of GCS, GGT, and GST-rr genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-77 were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.
Subject(s)
Humans , Blotting, Northern , Cisplatin , Doxorubicin , Drug Resistance , Glutathione , Metabolism , Parents , VincristineABSTRACT
Objective To study on glutathione and glutathione-related enzymes of Antarctic ice microalgae.Methods Glutathione(GSH) content,glutathione produce ability(GPA) and glutathione reductase(GR) activity in 24 kinds of Antarctic ice microalgae were assessed using the spectrophotometer methods.Results GSH content of Cyanophyceae B-1 was highest.Total GSH yields of Antarctic ice microalgae Chlamydomonas sp.ICE-L and Berkeleya rutilans GJ01 were in the top two positions.GPA in most Antarctic ice microalgae was higher than that in mesophilic green algae,and only in two ice microalgae was lower than that in Phaeodactylum tricornutum.GR activities of Antarctic ice microalgae Berkeleya rutilans GJ01 and Chlamydomonas sp.ICE-L were greater than that of the control microalgae.Conclusion It is possible that Antarctic ice microalgae will become a new resource of GSH.
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Object To investigate the mechanisms of action of lentinan (LTN) activated mouse peritoneal macrophages to produce nitric oxide (NO). Methods The effects of LTN on NO output and intracellular glutathione (GSH) in mouse peritoneal macrophages and the correlation of them were studied. Results (1) LTN can significantly increase production of NO in mouse peritoneal macrophages, decrease level of intracellular GSH followed increase of NO production. (2) The above effect can be blocked efficiently by the NO production inhibitors. (3) NO production can be inhibited by GSH lowering drugs. Conclusion LTN increase NO production with depletion of intracellular GSH in the activated mouse peritoneal macrophages. It suggested that intracellular GSH plays an important role in regulation of NO production and protection of host cells from cytotoxic attack induced by NO.
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BACKGROUND: N-acetylcysteine(ACE) is used both orally and intravenously in a variety of experimental pathologies resembling human disease states which exhibit endothelial toxicity as a result of oxidative stress, including acute pulmonary oxygen toxicity, septicemia and endotoxin shock. Despite these observations in vivo, it is not certain how this thiol drug produces its protective effects. ACE is a cysteine derivative which is able to directly react with oxygen radicals and may also act as a cysteine and glutathione(GSH) precursor following deacetylation. In this paper, we tried to know whether the therapeutic doses of ACE can modify the inflammatory function of the neutrophils and can increase the glutathione level of plasma in chronic obstructive pulmonary disease(COPD) patients. In addition, the effect of ACE to the purified neutrophil in terms of superoxide release and glutathione synthesis were observed. METHOD: Firstly, we gave 600mg of ACE for seven days and compare the release of superoxide, luminol-enhanced chemiluminescence from the neutrophils, neutrophil chemotaxis, and plasma GSH levels before and after ACE treatment in COPD patients. Secondly, we observed the dose dependent effect of ACE to the purified neutrophil's superoxide release and GSH levels in vitro. RESULTS: 1) Usual oral therapeutic doses(600mg per day) of ACE for seven days did affect neither on the neutrophils superoxide release, chemiluminescence, chemotaxis, nor on the plasma GSH concentration in the COPD patients. 2) ACE decreases the purified neutrophil's superoxide release and increase the GSH production in dose dependent fashion in vitro. CONCLUSION: Despite the fact that oral ACE treatment did not affect on the neutrophil's inflammatory function and plasma GSH concentration in COPD patients in usual therapeutic doses, it decreases the superoxide release and increases the GSH production from the isolated neutrophils in high molar concentrations. These findings suggest that to obtain an antioxidative effects of ACE, it might be needed to increase the daily dosage of ACE or therapeutic duration or change the route of adminisration in COPD patients.