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O-linked-N-acetylglucosamine (O-GlcNAc) modification is a unique post-translational modification that plays a regulatory role in many cellular processes, such as transcription, intracellular signaling, endocytosis, and protein stability. Epidermal growth factor (EGF) domain-specific O-GlcNAc transferase (EOGT) is an endoplasmic reticulum (ER) resident protein which can glycosylate the residues of Ser or Thr of secreted or membrane (transmembrane) glycoproteins containing EGF domain. Notch signaling pathway is involved in cell-to-cell communication which regulates cell biological processes through interactions between adjacent cells. To date, EOGT-mediated O-GlcNAc modification has been found to be involved in many human diseases, and shown significant relation with Notch signaling pathway. However, the specific molecular mechanisms have not been fully elucidated. In this review, we briefly introduce recent studies regarding to the roles of EOGT-mediated O-GlcNAc modification and its correlation with Notch signaling pathway in human diseases.
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Fungal biomass, being organic waste, could be an excellent source of protein, carbohydrate and minerals. However, it has not been exploited fully until now. Efficient management of this waste can not only address the environmental impact on its disposal but also yield value-added metabolites. In the present study, in order to explore its potential, we subjected dead fungal biomass of Aspergillus niger SKN1 as substrate for both fermentative and enzymatic biodegradation, respectively by potent proteo-chitinolytic bacteria Alcaligenes faecalis SK10 and its enzyme cocktail. The results revealed that reasonable amount of protease and chitinase could be biosynthesized by the fermentative mode of utilization, while a mixture of amino acid, peptides and low-molecular weight amino-sugar (mono and oligomeric form of N-acetylglucosamine) could be generated through enzymatic hydrolysis. The physicochemical condition of both the bioprocess was subsequently optimized through statistical approach. The projected utilization of waste zero-valued fungal biomass offer a sustainable and environmentally sound method for production of microbial metabolites and large scale execution of the same could be proficient and in tune with the principle of circular economy.
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Caveolin-1 (Cav-1), a major structural protein of caveolae, is implicated in the vesicular uptake processes of transcytosis and cell signaling. However, its role in modulating protein glycosylation and tumor metastasis remains to be further elucidated. In the present study, it was shown that Cav-1 promotes the expression of O-GlcNAcylation and O-GlcNAc transferase (OGT), and triggers the invasion and metastasis of hepatocellular carcinoma (HCC) cells. The results of RT-qPCR, Western blot and dual lucif-erase reporter assay showed that Cav-1 negatively regulated the expression of transcription factor RUNX2 in HCC. Subsequently, this results in attenuate RUNX2-induced transcription of miR24. miR24 suppresses mouse HCC cells invasion and metastasis via directly targeting Ogt mRNA 3′UTR. This research provides evidence of Cav-1-mediated OGT expression and O-GlcNAc (O-linked N-acetylglucosamine) elevation. These data give insight into a novel mechanism of HCC occurrence and development.
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Objective:To investigate the expressions of O-GlcNAc transferase (OGT) in the hepatocellular carcinoma (HCC) tissue,cells and serum,and to clarify the significance of OGT in diagnosis and treatment of HCC.Methods:Western blotting method was used to detect the expression levels of OGT in 20 samples of HCC tissue and matched non-tumor tissue,8 hepatoma cell lines and normal liver (human) cell lysate.The expression levels of serum OGT were detected by direct ELISA in 20 liver cirrhosis (LC) patients,20 HCC patients and 20 healthy volunteers.The relationship between the expression levels of protein in HCC tissue,cells and serum and the occurrence and development of tumor were analyzed.Results:The Western blotting results showed there were expressions of OGT in both HCC tissue and matched non-tumor tissue;The positive expression rate of OGT in HCC tissue was significantly higher than that in non-tumor tissue (P＜0.05).There were expressions of OGT in both hepatoma cell lines and normal liver (human) cell lysate;the positive expression rate of OGT in HCC cell lysate was significantly higher than that in the normal liver cell lysate (P＜0.05).The result of direct ELISA showed that the serum OGT levels of the LC and HCC patients were equally higher than that of the healthy volunteers (P＜0.05).Conclusion:OGT highly expresses in HCC tissue and OGT is a promising biomarker for the diagnosis of HCC.
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Objective:To investigate the expressions of O-GlcNAc transferase (OGT) in the hepatocellular carcinoma (HCC) tissue,cells and serum,and to clarify the significance of OGT in diagnosis and treatment of HCC.Methods:Western blotting method was used to detect the expression levels of OGT in 20 samples of HCC tissue and matched non-tumor tissue,8 hepatoma cell lines and normal liver (human) cell lysate.The expression levels of serum OGT were detected by direct ELISA in 20 liver cirrhosis (LC) patients,20 HCC patients and 20 healthy volunteers.The relationship between the expression levels of protein in HCC tissue,cells and serum and the occurrence and development of tumor were analyzed.Results:The Western blotting results showed there were expressions of OGT in both HCC tissue and matched non-tumor tissue;The positive expression rate of OGT in HCC tissue was significantly higher than that in non-tumor tissue (P＜0.05).There were expressions of OGT in both hepatoma cell lines and normal liver (human) cell lysate;the positive expression rate of OGT in HCC cell lysate was significantly higher than that in the normal liver cell lysate (P＜0.05).The result of direct ELISA showed that the serum OGT levels of the LC and HCC patients were equally higher than that of the healthy volunteers (P＜0.05).Conclusion:OGT highly expresses in HCC tissue and OGT is a promising biomarker for the diagnosis of HCC.
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Objective@#To explore the effects of O-GlcNAc glycosylation and its key enzyme OGT on the biological behaviors and etoposide (Vp16) -induced apoptosis of Nalm-6 cells.@*Methods@#Low O-GlcNAc modified Nalm-6 cells model was established with Alloxan, an inhibitor of OGT. The influence of Alloxan on Nalm-6 cells proliferation was checked by CCK-8 assay, apoptosis and cell cycle by flow cytometry. Nalm-6 cells were treated with different concentrations of Vp16 for 12 h, and then the O-GlcNAc level and the expressions of OGT were examined by Western blot. After treating Nalm-6 with Alloxan for 24 h and then 5 μg/ml of Vp16 for 12 h, the apoptosis of different groups were measured with flow cytometry, and the expression of apoptosis-associated proteins Bax and Bcl-2 were examined by Western blot.@*Results@#With the concentration of Vp16 increasing, the O-GlcNAc modified levels of total protein and the expression of OGT were up regulated (P<0.05, n=6) ; Alloxan could slow down the proliferation capacity, induce apoptosis[ (15.190±2.539) % vs (21.910±4.105) %, P=0.007], arrest cell cycle[G1 phase: (43.534±4.453) % vs (57.322±6.091) %, P=0.003; S phase: (50.747±5.937) % vs (37.201±4.661) %, P=0.001]. Alloxan could inhibit the apoptosis caused by Vp16[ (75.195±13.845) % vs (52.741±10.815) %, P=0.011]along with Bax decreasing (5.496±1.998 vs 2.950±0.703, P=0.015) and Bcl-2 increasing (0.454±0.125 vs 0.803±0.223, P=0.013) .@*Conclusion@#Changes of O-GlcNAc modified level of Nalm-6 cells along with the inhibition of OGT could influence the biological behaviors and inhibit apoptosis induced by Vp16.
ABSTRACT
O-GlcNAcylation is the addition of a single N-acetylglucosamine (GlcNAc) moiety to the hydroxyl groups of serine or threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc plays an important role in the regulation of many biological processes including, but not limited to, cell cycle progression, transcription, translation, signal transduction, stress response, etc. O-GlcNAc plays significant roles in the progression and etiology of various diseases including diabetes, cardiovascular disease, cancer and Alzheimer's disease. The aberrant O-GlcNAcylation in tumor tissues is closely associated with cell proliferation and metastasis. This review is mainly involved the characteristics of protein O-GlcNAcylation alterations in different types of human cancer and the functions of O-GlcNAcylation in oncogenes and tumor suppressor genes. Copyright © 2013 by TUMOR.
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Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs) forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM) and NEM analogs along with a cationic polypeptide protamine sulfate (PS), which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM) and protamine sulfate (PS) on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI). Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml) was combined with protamine sulfate (50 μg/ml) and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a significant synergistic inhibitory effect on Staphylococcus aureus and Enterococcus spp., whereas Pseudomonas aeruginosa and Klebsiella pneumoniae remained unaffected. Combination of GlmU inhibitor-plus-protamine sulfate failed to significantly reduce bacterial adherence of Pseudomonas aeruginosa and Klebsiella pneumoniae to catheter and cannula pieces, respectively. We found that the GlmU inhibitor was mainly effective in preventing the adherence and biofilm formation by gram-positive organisms. The combination of NEM and protamine sulfate may, therefore, be tried as anti-infective coatings for medical devices such as catheters and cannulas, and thus help in overcoming microbial resistance in the current era of increasing device-associated hospital infections.
Subject(s)
Bacterial Adhesion/drug effects , Biofilms/drug effects , Catheters/adverse effects , Catheters/microbiology , Cross Infection/microbiology , Cross Infection/prevention & control , Ethylmaleimide/analogs & derivatives , Multienzyme Complexes , N-Ethylmaleimide-Sensitive Proteins , Nucleotidyltransferases , Protamines , Surface PropertiesABSTRACT
ibits tyrosinase activity and melanogenesis in murine B16 melanoma cells. Hence, N-acetylglucosamine may serve as a skin lightening agent in the future.
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Nonaka myopathy (NM) or distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessively inherited neuromuscular disorder characterized by early adult-onset weakness of distal muscles, rimmed vacuoles in muscle biopsy, and mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. The authors describe a patient with typical clinical features of NM confirmed by GNE mutation. Mutation analysis of the GNE gene revealed that the patient was a compound heterozygous for V572L and C13S mutations.
Subject(s)
Humans , Biopsy , Distal Myopathies , Muscles , Muscular Diseases , Phosphotransferases , VacuolesABSTRACT
Nonaka myopathy (NM) or distal myopathy with rimmed vacuoles was an autosomal recessive muscle disease with preferential involvement of the tibialis anterior and sparing quadriceps muscles in young adulthood. Patients with NM usually showed slightly elevated serum creatine kinase (CK) levels and characteristic rimmed vacuoles in muscle biopsy. Recently, the UDP-N-acetylglucosamine-2-epimerase/N-ace-tylmannosamine kinase (GNE) gene was identified as the identified as the causative gene for NM. Here we reported a NM patient carrying homozygous mutations (V572L) of the GNE gene. To the best of our knowledge, this was the first report of genetically confirmed NM in Korea and NM should be included in the differential diagnosis of slowly progressive weakness of distal legs.