Search results for "Glycogen"
showing 10 items of 189 documents
Expanding the clinical spectrum of late-onset Pompe disease: Dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered
2011
Abstract Purpose Cerebro-vascular arteriopathy has been reported in late-onset Pompe disease (LOPD). Evidence of increased aortic stiffness in some patients and smooth muscle involvement in LOPD raises the possibility of aortic involvement. Our aim was to determine if aortic arteriopathy may be a complication of LOPD. Methods One patient with LOPD was diagnosed with aortic dilatation at Duke Metabolic clinic, 4 others were diagnosed at University of Mainz, Germany, where chest X-ray and echocardiography are routinely done for patients. Other causes of aortic vascular disease were assessed. Results We report evidence of dilated arteriopathy involving primarily the ascending thoracic aorta in…
Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity
2012
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors.
2007
International audience; Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2…
Small round blue cell sarcoma of bone mimicking atypical Ewing's sarcoma with neuroectodermal features. An analysis of five cases with immunohistoche…
1987
Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a …
Amyloid-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease.
2011
Amyloid-β peptide (Aβ) toxicity and tau hyperphosphorylation are hallmarks of Alzheimer’s disease (AD). How their molecular relationships may affect the etiology, progression, and severity of the disease, however, has not been elucidated. We now report that incubation of foetal rat cortical neurons with Aβ up-regulates expression of the Regulator of Calcineurin gene RCAN1, and this is mediated by Aβ-induced oxidative stress. Calcineurin (PPP3CA) is a serine-threonine phosphatase that dephosphorylates tau. RCAN1 proteins inhibit this phosphatase activity of calcineurin. Increased expression of RCAN1 also causes up-regulation of glycogen synthase kinase-3beta (GSK3β), a tau kinase. Thus, incr…
Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoG…
2019
This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths…
GSK-3? Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutra…
2021
Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed wi…
Modeling a Novel Variant of Glycogenosis IXa Using a Clonal Inducible Reprogramming System to Generate "Diseased" Hepatocytes for Accurate Diagnosis.
2022
The diagnosis of inherited metabolic disorders is a long and tedious process. The matching of clinical data with a genomic variant in a specific metabolic pathway is an essential step, but the link between a genome and the clinical data is normally difficult, primarily for new missense variants or alterations in intron sequences. Notwithstanding, elucidation of the pathogenicity of a specific variant might be critical for an accurate diagnosis. In this study, we described a novel intronic variant c.2597 + 5G > T in the donor splice sequence of the PHKA2 gene. To investigate PHKA2 mRNA splicing, as well as the functional consequences on glycogen metabolism, we generated hepatocyte-like ce…
Sublethal Effects of an Organophosphate Insecticide on the European Eel,Anguilla anguilla
1997
The present communication deals with the effects of fenitrothion (0.02 mg/liter) on the energy metabolism of the European eel, Anguilla anguilla, and its recovery from intoxication. Various parameters such as glycogen, lactate, proteins, and glucose levels were measured in different eel tissues after 2, 8, 12, 24, 32, 48, 56, 72, and 96 hr of fenitrothion exposure. Subsequently, the fish were allowed recovery periods of 8, 12, 24, 48, 72, 96, 144, and 192 hr in clean water, and the same parameters were evaluated. Liver glycogen content showed no significant changes during the exposure time, while blood glucose levels increased markedly. Gill, liver, and blood lactate values increased during…
Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes
2014
Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver gluc…