Only in Titles

Search results for: OGT

paperclip

Error loading info... Pleas try again later.
paperclip

#33609540   2021/02/17 To Up

O-linked N-acetylglucosaminyltransferase OGT inhibits diabetic nephropathy by stabilizing histone methyltransferases EZH2 via the HES1/PTEN axis.

O-linked N-acetylglucosaminyltransferase (OGT) is involved in diabetes-related diseases including diabetic nephropathy (DN), and responsible for O-GlcNAcylation. Moreover, O-GlcNAcylation and OGT could be induced by high glucose. Thus, we sought to explore the molecular mechanism of OGT in DN.
Na Fang, Ping Li

1746 related Products with: O-linked N-acetylglucosaminyltransferase OGT inhibits diabetic nephropathy by stabilizing histone methyltransferases EZH2 via the HES1/PTEN axis.

100 µg1mg1 mg 0.1 mg 500 tests50мg/vial100 ul100ul100 ul96 assays

Related Pathways

paperclip

#33597927   2021/02/01 To Up

Centrosomes: Til O-GlcNAc Do Us Apart.

The centrosome apparatus is vital for spindle assembly and chromosome segregation during mitotic divisions. Its replication, disjunction and separation have to be fine-tuned in space and time. A multitude of post-translational modifications (PTMs) have been implicated in centrosome modulation, including phosphorylation, ubiquitination and acetylation. Among them is the emerging O-linked N-acetylglucosamine (O-GlcNAc) modification. This quintessential PTM has a sole writer, O-GlcNAc transferase (OGT), and the only eraser, O-GlcNAcase (OGA). O-GlcNAc couples glucose metabolism with signal transduction and forms a yin-yang relationship with phosphorylation. Evidence from proteomic studies as well as single protein investigations has pinpointed a role of O-GlcNAc in centrosome number and separation, centriole number and distribution, as well as the cilia machinery emanating from the centrosomes. Herein we review our current understanding of the sweet modification embedded in centrosome dynamics and speculate that more molecular details will be unveiled in the future.
Aiyun Yuan, Xiangyan Tang, Jing Li

2019 related Products with: Centrosomes: Til O-GlcNAc Do Us Apart.

100ug Lyophilized100ug96T100ug Lyophilized100μg100ml1 ea 100ul10 mg100 mg100 ug

Related Pathways

paperclip

#33593071   2021/02/17 To Up

Excessive - GlcNAcylation Causes Heart Failure and Sudden Death.

Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension and diabetes. -GlcNAcylation is a post-translational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. The total levels of -GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of two enzymes, -GlcNAc transferase (OGT) and -GlcNAcase (OGA). Failing myocardium is marked by increased -GlcNAcylation, but it is unknown if excessive -GlcNAcylation contributes to cardiomyopathy and heart failure. We developed two new transgenic mouse models with myocardial overexpression of OGT and OGA to control -GlcNAcylation independent of pathological stress. We found that OGT transgenic hearts showed increased -GlcNAcylation, and developed severe dilated cardiomyopathy, ventricular arrhythmias and premature death. In contrast, OGA transgenic hearts had lower -GlcNAcylation but identical cardiac function to wild type littermate controls. Additionally, OGA transgenic hearts were resistant to pathological stress induced by pressure overload with attenuated myocardial -GlcNAcylation levels after stress and decreased pathological hypertrophy compared to wild type controls. Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in -GlcNAc mediated cardiac pathology. Our data provide evidence that excessive -GlcNAcylation causes cardiomyopathy, at least in part, due to defective energetics. Enhanced OGA activity is well tolerated and attenuation of -GlcNAcylation is beneficial against pressure overload induced pathologic remodeling and heart failure. These findings suggest attenuation of excessive -GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy.
Priya Umapathi, Partha S Banerjee, Natasha E Zachara, Neha Abrol, Qinchuan Wang, Olurotimi O Mesubi, Elizabeth D Luczak, Yuejin Wu, Jonathan M Granger, An-Chi Wei, Oscar E Reyes Gaido, Liliana Florea, C Conover Talbot, Gerald W Hart, Mark E Anderson

1347 related Products with: Excessive - GlcNAcylation Causes Heart Failure and Sudden Death.

25 mg0.25 mg100ug10 mg100ug100ug Lyophilized500 MG100ug Lyophilized25 mg1 mL50 ug 96T

Related Pathways

paperclip

#33592173   2021/02/09 To Up

A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation.

The architecture of cristae provides a spatial mitochondrial organization that contains functional respiratory complexes. Several protein components including OPA1 and MICOS complex subunits organize cristae structure, but upstream regulatory mechanisms are largely unknown. Here, in vivo and in vitro reconstitution experiments show that the endoplasmic reticulum (ER) kinase PERK promotes cristae formation by increasing TOM70-assisted mitochondrial import of MIC19, a critical subunit of the MICOS complex. Cold stress or β-adrenergic stimulation activates PERK that phosphorylates O-linked N-acetylglucosamine transferase (OGT). Phosphorylated OGT glycosylates TOM70 on Ser94, enhancing MIC19 protein import into mitochondria and promoting cristae formation and respiration. In addition, PERK-activated OGT O-GlcNAcylates and attenuates CK2α activity, which mediates TOM70 Ser94 phosphorylation and decreases MIC19 mitochondrial protein import. We have identified a cold-stress inter-organelle PERK-OGT-TOM70 axis that increases cell respiration through mitochondrial protein import and subsequent cristae formation. These studies have significant implications in cellular bioenergetics and adaptations to stress conditions.
Pedro Latorre-Muro, Katherine E O'Malley, Christopher F Bennett, Elizabeth A Perry, Eduardo Balsa, Clint D J Tavares, Mark Jedrychowski, Steven P Gygi, Pere Puigserver

2403 related Products with: A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation.

100ul100ul 100ul100ug1000 TESTS/0.65ml100ug100ug100ug5001 Set1 Set2

Related Pathways

paperclip

#33576380   2021/02/08 To Up

Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart.

The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery.
Darnel Prakoso, Shiang Y Lim, Jeffrey R Erickson, Rachel S Wallace, Jarmon G Lees, Mitchel Tate, Helen Kiriazis, Daniel G Donner, Darren C Henstridge, Jonathan R Davey, Hongwei Qian, Minh Deo, Laura J Parry, Amy J Davidoff, Paul Gregorevic, John C Chatham, Miles J De Blasio, Rebecca H Ritchie

1264 related Products with: Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart.

100.00 ul12000 IU500 Units10 100 G0.1 mg

Related Pathways

paperclip

#33575132   2021/01/28 To Up

Metabolic impact of weight variations in Icelandic horses.

Insulin dysregulation (ID) is an equine endocrine disorder, which is often accompanied by obesity and various metabolic perturbations. The relationship between weight variations and fluctuations of the insulin response to oral glucose tests (OGT) as well as the metabolic impact of ID have been described previously. The present study seeks to characterize the concomitant metabolic impact of variations in the insulin response and bodyweight during repeated OGTs using a metabolomics approach.
Julien Delarocque, Florian Frers, Korinna Huber, Klaus Jung, Karsten Feige, Tobias Warnken

1888 related Products with: Metabolic impact of weight variations in Icelandic horses.

500 gm.100μg2ug100ug100 50 ug1 Set100 1 Set1 Set1 Set

Related Pathways

paperclip

#33550377   2021/02/08 To Up

Evidence and manipulation of O-GlcNAcylation in granulosa cells of bovine antral follicles.

Glucose is a preferred energy substrate for metabolism by bovine granulosa cells (GCs). O-linked N-acetylglucosaminylation (O-GlcNAcylation), is a product of glucose metabolism that occurs as the hexosamine biosynthesis pathway (HBP) shunts O-GlcNAc sugars to serine and threonine residues of proteins. O-GlcNAcylation through the HBP is considered a nutrient sensing mechanism that regulates many cellular processes. Yet little is known of its importance in GCs. Here, O-GlcNAcylation in GCs and its effects on GC proliferation were determined. Bovine ovaries from an abattoir, staged to the mid-to-late estrous period were used. Follicular fluid and GCs were aspirated from small (3-5 mm) and large (>10 mm) antral follicles. Freshly isolated GCs of small follicles exhibited greater expression of O-GlcNAcylation and O-GlcNAc transferase (OGT) than large follicles. Less glucose and more lactate was detectable in the follicular fluid of small versus large follicles. Culture of GCs revealed that inhibition of the HBP via the glutamine fructose-6-phosphate aminotransferase inhibitor, DON (50 μM), impaired O-GlcNAcylation and GC proliferation, regardless of follicle size. Direct inhibition of O-GlcNAcylation via the OGT inhibitor, OSMI-1 (50 μM), also prevented proliferation, but only in GCs of small follicles. Augmentation of O-GlcNAcylation via the O-GlcNAcase inhibitor, Thiamet-G (2.5 μM), had no effect on GC proliferation, regardless of follicle size. The results indicate GCs of bovine antral follicles undergo O-GlcNAcylation, and O-GlcNAcylation is associated with alterations of glucose and lactate in follicular fluid. Disruption of O-GlcNAcylation impairs GC proliferation. Thus, the HBP via O-GlcNAcylation constitutes a plausible nutrient-sensing pathway influencing bovine GC function and follicular growth.
Abigail M Maucieri, David H Townson

1508 related Products with: Evidence and manipulation of O-GlcNAcylation in granulosa cells of bovine antral follicles.

1.00 flask100ml30ml500 ml96 tests500 ml 5 G

Related Pathways

paperclip

#33544938   2021/02/05 To Up

Metabolic sensor O-GlcNAcylation regulates megakaryopoiesis and thrombopoiesis through c-Myc stabilization and integrin perturbation.

Metabolic state of hematopoietic stem cells (HSCs) is an important regulator of self-renewal and lineage-specific differentiation. Posttranslational modification of proteins via O-GlcNAcylation is an ideal metabolic sensor, but how it contributes to megakaryopoiesis and thrombopoiesis remains unknown. Here, we reveal for the first time that cellular O-GlcNAcylation levels decline along the course of megakaryocyte (MK) differentiation from human-derived hematopoietic stem and progenitor cells (HSPCs). Inhibition of O-GlcNAc transferase (OGT) that catalyzes O-GlcNAcylation prolongedly decreases O-GlcNAcylation and induces the acquisition of CD34 CD41a MK-like progenitors and its progeny CD34 CD41a /CD42b megakaryoblasts (MBs)/MKs from HSPCs, consequently resulting in increased CD41a and CD42b platelets. Using correlation and co-immunoprecipitation analyses, we further identify c-Myc as a direct downstream target of O-GlcNAcylation in MBs/MKs and provide compelling evidence on the regulation of platelets by novel O-GlcNAc/c-Myc axis. Our data indicate that O-GlcNAcylation posttranslationally regulates c-Myc stability by interfering with its ubiquitin-mediated proteasomal degradation. Depletion of c-Myc upon inhibition of OGT promotes platelet formation in part through the perturbation of cell adhesion molecules, that is, integrin-α4 and integrin-β7, as advised by gene ontology and enrichment analysis for RNA sequencing and validated herein. Together, our findings provide a novel basic knowledge on the regulatory role of O-GlcNAcylation in megakaryopoiesis and thrombopoiesis that could be important in understanding hematologic disorders whose etiology are related to impaired platelet production and may have clinical applications toward an ex vivo platelet production for transfusion.
Sudjit Luanpitpong, Jirarat Poohadsuan, Phatchanat Klaihmon, Xing Kang, Kantpitchar Tangkiettrakul, Surapol Issaragrisil

2146 related Products with: Metabolic sensor O-GlcNAcylation regulates megakaryopoiesis and thrombopoiesis through c-Myc stabilization and integrin perturbation.

10 mg100ug500 mg1000 25 mg 5 G100ul1 ml25 mg 5 G100ug1 g

Related Pathways

paperclip

#33543027   2020/02/29 To Up

Induction of heparanase via IL-10 correlates with a high infiltration of CD163+ M2-type tumor-associated macrophages in inflammatory breast carcinomas.

Inflammatory breast cancer (IBC) is the most aggressive and lethal form of breast cancer, characterized by a high infiltration of tumor-associated macrophages and poor prognosis. To identify new biomarkers and to elucidate the molecular mechanisms underlying IBC pathogenesis, we investigated the expression pattern of heparanase (HPSE) and its activator cathepsin L (CTSL). First, we quantitated the and mRNA levels in a cohort of breast cancer patients after curative surgery (20 IBC and 20-non-IBC). We discovered that both and mRNA levels were significantly induced in IBC tissue vis-à-vis non-IBC patients ( <0 .05 and  <0 .001, respectively). According to the molecular subtypes, mRNA levels were significantly higher in carcinoma tissues of triple negative (TN)-IBC as compared to TN-non-IBC ( <0 .05). Mechanistically, we discovered that pharmacological inhibition of HPSE activity resulted in a significant reduction of invasiveness in the IBC SUM149 cell line. Moreover, siRNA-mediated HPSE knockdown significantly downregulated the expression of the metastasis-related gene MMP2 and the cancer stem cell marker CD44. We also found that IBC tumors revealed robust heparanase immune-reactivity and CD163+ M2-type tumor-associated macrophages, with a positive correlation of both markers. Moreover, the secretome of axillary tributaries blood IBC CD14+ monocytes and the cytokine IL-10 significantly upregulated mRNA and protein expression in SUM149 cells. Intriguingly, massively elevated mRNA expression with a trend of positive correlation with mRNA expression was detected in carcinoma tissue of IBC. Our findings highlight a possible role played by CD14+ monocytes and CD163+ M2-type tumor-associated macrophages in regulating expression possibly via IL-10. Overall, we suggest that heparanase, cathepsin L and CD14+ monocytes-derived IL-10 may play an important role in the pathogenesis of IBC and their targeting could have therapeutic implications.
Mennatullah El-Nadi, Hebatallah Hassan, Moshira Ezzat Saleh, Eyyad Nassar, Yahia Mahmoud Ismail, Mahmoud Amer, Burkhard Greve, Martin Götte, Mohamed El-Shinawi, Sherif Abdelaziz Ibrahim

1503 related Products with: Induction of heparanase via IL-10 correlates with a high infiltration of CD163+ M2-type tumor-associated macrophages in inflammatory breast carcinomas.



Related Pathways