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Glycogen Accumulation (glycogen + accumulation)
Selected AbstractsEnhanced glycogenesis is involved in cellular senescence via GSK3/GS modulationAGING CELL, Issue 6 2008Yong-Hak Seo Summary Glycogen biogenesis and its response to physiological stimuli have often been implicated in age-related diseases. However, their direct relationships to cell senescence and aging have not been clearly elucidated. Here, we report the central involvement of enhanced glycogenesis in cellular senescence. Glycogen accumulation, glycogen synthase (GS) activation, and glycogen synthase kinase 3 (GSK3) inactivation commonly occurred in diverse cellular senescence models, including the liver tissues of aging F344 rats. Subcytotoxic concentrations of GSK3 inhibitors (SB415286 and LiCl) were sufficient to induce cellular senescence with increased glycogenesis. Interestingly, the SB415286-induced glycogenesis was irreversible, as were increased levels of reactive oxygen species and gain of senescence phenotypes. Blocking GSK3 activity using siRNA or dominant negative mutant (GSK3,-K85A) also effectively induced senescence phenotypes, and GS knock-down significantly attenuated the stress-induced senescence phenotypes. Taken together, these results clearly demonstrate that augmented glycogenesis is not only common, but is also directly linked to cellular senescence and aging, suggesting GSK3 and GS as novel modulators of senescence, and providing new insight into the metabolic backgrounds of aging and aging-related pathogenesis. [source] AMP-activated protein kinase: a core signalling pathway in the heartACTA PHYSIOLOGICA, Issue 1 2009A. S. Kim Abstract Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory ,2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy. [source] Role of reserve carbohydrates in the growth dynamics of Saccharomyces cerevisiae,FEMS YEAST RESEARCH, Issue 8 2004Vincent Guillou Abstract The purpose of this study was to explore the role of glycogen and trehalose in the ability of Saccharomyces cerevisiae to respond to a sudden rise of the carbon flux. To this end, aerobic glucose-limited continuous cultures were challenged with a sudden increase of the dilution rate from 0.05 to 0.15 h,1. Under this condition, a rapid mobilization of glycogen and trehalose was observed which coincided with a transient burst of budding and a decrease of cell biomass. Experiments carried out with mutants defective in storage carbohydrates indicated a predominant role of glycogen in the adaptation to this perturbation. However, the real importance of trehalose in this response was veiled by the unexpected phenotypes harboured by the tps1 mutant, chosen for its inability to synthesize trehalose. First, the biomass yield of this mutant was 25% lower than that of the isogenic wild-type strain at dilution rate of 0.05 h,1, and this difference was annulled when cultures were run at a higher dilution rate of 0.15 h,1. Second, the tps1 mutant was more effective to sustain the dilution rate shift-up, apparently because it had a faster glycolytic rate and an apparent higher capacity to consume glucose with oxidative phosphorylation than the wild type. Consequently, a tps1gsy1gsy2 mutant was able to adapt to the dilution rate shift-up after a long delay, likely because the detrimental effects from the absence of glycogen was compensated for by the tps1 mutation. Third, a glg1,glg2, strain, defective in glycogen synthesis because of the lack of the glycogen initiation protein, recovered glycogen accumulation upon further deletion of TPS1. This recovery, however, required glycogen synthase. Finally, we demonstrated that the rapid breakdown of reserve carbohydrates triggered by the shift-up is merely due to changes in the concentrations of hexose-6-phosphate and UDPglucose, which are the main metabolic effectors of the rate-limiting enzymes of glycogen and trehalose pathways. [source] Differential effects of dihalogenated and trihalogenated acetates in the liver of B6C3F1 miceJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001J. Kato-Weinstein Abstract Haloacetates are produced in the chlorination of drinking water in the range 10,100 ,g l,1. As bromide concentrations increase, brominated haloacetates such as bromodichloroacetate (BDCA), bromochloroacetate (BCA) and dibromoacetate (DBA) appear at higher concentrations than the chlorinated haloacetates: dichloroacetate (DCA) or trichloroacetate (TCA). Both DCA and TCA differ in their hepatic effects; TCA produces peroxisome proliferation as measured by increases in cyanide-insensitive acyl CoA oxidase activity, whereas DCA increases glycogen concentrations. In order to determine whether the brominated haloacetates DBA, BCA and BDCA resemble DCA or TCA more closely, mice were administered DBA, BCA and BDCA in the drinking water at concentrations of 0.2,3 g l,1. Both BCA and DBA caused liver glycogen accumulation to a similar degree as DCA (12 weeks). The accumulation of glycogen occurred in cells scattered throughout the acinus in a pattern very similar to that observed in control mice. In contrast, TCA and low concentrations of BDCA (0.3 g l,1) reduced liver glycogen content, especially in the central lobular region. The high concentration of BDCA (3 g l,1) produced a pattern of glycogen distribution similar to that in DCA-treated and control mice. This effect with a high concentration of BDCA may be attributable to the metabolism of BDCA to DCA. All dihaloacetates reduced serum insulin levels. Conversely, trihaloacetates had no significant effects on serum insulin levels. Dibromoacetate was the only brominated haloacetate that consistently increased acyl-CoA oxidase activity and rates of cell replication in the liver. These results further distinguish the effects of the dihaloacetates from those of peroxisome proliferators like TCA. Copyright © 2001 John Wiley & Sons, Ltd. [source] Evaluation of Experimental and Practical Diets for Walleye Stizostedion vitreumJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2002Anant S. Bharadwaj Culture of walleye Sfizostedion vitreum is one of the largest components of public sector aquaculture in the eastern U.S. and there is increasing interest in private sector culture. However, the nutritional requirements of walleye are unknown and experimental diets for use in quantifying nutritional requirements have not been identified. We formulated four experimental and four practical diets and fed those to triplicate groups of walleye with an initial weight of 13 g per fish. The experimental diets contained either casein (CAS), casein + gelatin (CG), casein + arginine (CA), or casein + gelatin + crystalline amino acids (CGAA) as sources of amino acids. The practical diets were formulated to mimic salmon grower (SG) and trout grower (TG) diets, a fish meal-free diet for trout (TFMF), and a walleye grower (WG) diet. Fish were fed twice daily to satiation for 9 wk. Feed consumption, percent weight gain, specific growth rates, feed efficiency, protein efficiency ratio, and protein retention efficiency were not significantly different among fish fed CGAA, SG, and TG, but those values were significantly higher than in fish fed other diets. Weight gain of fish fed CGAA was approximately 80% of that in fish fed SG and 91% of that in fish fed TG. Protein retention efficiency of fish fed CGAA was approximately 69% and 81% of that observed for fish fed SG, and TG, respectively. In general, the carcasses of fish fed diets CGAA, SG and TG had significantly lower moisture and ash concentrations, and higher lipid levels than fish fed other diets. There were no significant differences in carcass protein concentration, muscle proximate composition, or liver lipid concentration among treatments. Livers from fish fed all diets were characterized by microvesicular degeneration and glycogen accumulation in hepatocytes. Results from the study indicate that CGAA can be used as a basal experimental diet in future nutritional research with juvenile walleye and confirms the benefits of trout and salmon grower diets. Fish meal-free diets formulated around the requirements for rainbow trout were consumed at approximately 80% of the values in fish fed TG and SG, but weight gain was approximately 20% of that in fish fed TG and SG. It appears the nutritional requirements for walleye are different than those of rainbow trout. [source] Crystallization of the glycogen-binding domain of the AMP-activated protein kinase , subunit and preliminary X-ray analysisACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2005Galina Polekhina AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolism in response to energy demand and supply by adjusting the ATP-generating and ATP-consuming pathways. AMPK potentially plays a critical role in diabetes and obesity as it is known to be activated by metforin and rosiglitazone, drugs used for the treatment of type II diabetes. AMPK is a heterotrimer composed of a catalytic , subunit and two regulatory subunits, , and ,. Mutations in the , subunit are known to cause glycogen accumulation, leading to cardiac arrhythmias. Recently, a functional glycogen-binding domain (GBD) has been identified in the , subunit. Here, the crystallization of GBD in the presence of ,-cyclodextrin is reported together with preliminary X-ray data analysis allowing the determination of the structure by single isomorphous replacement and threefold averaging using in-house X-ray data collected from a selenomethionine-substituted protein. [source] Rhabdomyoma of the head and neck: Clinicopathologic features of two casesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2003Gianfranco Favia MD Abstract Background. Extracardiac rhabdomyomas are rare benign tumors of the head and neck. They are frequently misdiagnosed and possibly overtreated when confused with other aggressive tumors. Methods. This article reports on the clinicopathologic features of two such tumors affecting adult patients and initially seen as slowly-growing, indolent neoplasms. Results. The tumors were of fibrous consistency, mobile, with well-demarcated borders and evident lines of cleavage. Both patients were treated by conservative surgery and remained disease-free after prolonged clinical observation. Histologically, both tumors were composed of large eosinophilic cells intermingled with polyhedral clear cells. Both cell types contained abundant glycogen accumulations. Conclusions. The differential diagnosis is with granular cell tumor and with sarcomas, the former being easily distinguishable morphologically, and the latter be seen with more rapid growth and adherence to the adjacent tissues. On the basis of the preceding features, rhabdomyomas can be suspected at a preoperative stage and adequately managed with enucleation or simple excision. © 2003 Wiley Periodicals, Inc. Head Neck 25: 700,704, 2003 [source] Cytochemical and ultrastructural characterization of growing colonies of human embryonic stem cellsJOURNAL OF ANATOMY, Issue 4 2004Kohei Johkura Abstract The morphology of human embryonic stem (ES) cells changes with their colonial growth. For a better understanding of the growth of ES cell colonies in culture, we determined their cytochemical and ultrastructural characteristics focusing on images of living cells under a phase contrast microscope. During the initial growth stages, the colonies exhibited a mosaic appearance with discernible cell,cell borders. PAS staining coupled with amylase digestion demonstrated that the bright granules and dark deposits in the cytoplasm contained glycogen. Ultrastructurally they were glycogen accumulations, and clustered open spaces associated with various amounts of glycogen. Although intercellularly heterogeneous, these structures were detectable throughout colony growth. As the colonies grew, compaction towards the centre emerged and increased, accompanied by heterogeneous increases in coarse particles with or without a halo. TUNEL showed these particles to consist at least in part of apoptotic cells/bodies. Transmission electron microscopy indicated that most apoptotic cells had been phagocytosed by intact ES cells. Spontaneous differentiation was detected occasionally in the periphery of the colonies. The presence of PAS-positive fibrous structures not susceptible to amylase digestion and laminin-immunoreactivity indicated the accumulation of extracellular matrix in the peripheral differentiated areas. These findings made it possible to determine the growth stage of human ES cell colonies. [source] | |||||||||||||