Glycogen Degradation Research Articles

Acute and Chronic Phases of Complex Regional Pain Syndrome in Mice are Accompanied by Distinct Transcriptional Changes in the Spinal Cord

BackgroundCRPS is a painful, debilitating, and often-chronic condition characterized by various sensory, motor, and vascular disturbances. Despite many years of study, current treatments are limited by our understanding of the underlying mechanisms. Little is known on the molecular level concerning changes in gene expression supporting the nociceptive sensitization commonly observed in CRPS limbs, or how those changes might evolve over time.ResultsWe used a well-characterized mouse tibial fracture/cast immobilization model of CRPS to study molecular, vascular and nociceptive changes. We observed that the acute (3 weeks after fracture) and chronic (7 weeks after fracture) phases of CRPS-like changes in our model were accompanied by unique alterations in spinal gene expression corresponding to distinct canonical pathways. For the acute phase, top regulated pathways were: chemokine signaling, glycogen degradation, and cAMP-mediated signaling; while for the chronic phase, the associated pathways were: coagulation system, granzyme A signaling, and aryl hydrocarbon receptor signaling. We then focused on the role of CcL2, a chemokine that we showed to be upregulated at the mRNA and protein levels in spinal cord tissue in our model. We confirmed its association with the nociceptive sensitization displayed in this model by demonstrating that the spinal but not peripheral administration of a CCR2 antagonist (RS504393) in CRPS animals could decrease mechanical allodynia. The spinal administration of CcL2 itself resulted in mechanical allodynia in control mice.ConclusionsOur data provide a global look at the transcriptional changes in the spinal cord that accompany the acute and chronic phases of CRPS as modeled in mice. Furthermore, it follows up on one of the top-regulated genes coding for CcL2 and validates its role in regulating nociception in the fracture/cast model of CRPS.

Dos nuevas mutaciones en el gen que codifica la alfa-glucosidasa ácida en un adolescente con enfermedad de Pompe de inicio tardío

INTRODUCTION. Glycogen storage disease type II, or Pompe disease, is a lysosomal disease with an autosomal recessive pattern of inheritance. Late-onset Pompe disease is a progressive metabolic myopathy caused by decreased activity of the enzyme acid alpha-glucosidase (GAA), which gives rise to reduced degradation and later accumulation of glycogen in the lysosomes and cell cytoplasm. CASE REPORT. A 16-year-old Venezuelan male, diagnosed with late-onset glycogen storage disease type II, or Pompe disease, based on the patient's clinical picture and the biochemical findings. The patient presented unmistakable signs of muscular atrophy in the upper and lower limbs, as well as positive Gowers' sign. Levels of creatinkinase in serum were high. His functional respiratory capacity was diminished. The quantification of the enzymatic activity of acid alpha-glucosidase on filter paper did not show any significant decrease in activity. A molecular genetic analysis revealed the existence of two homozygotic mutations in the gene GAA, c.547-67C>G and c.547-39T>G, both on exon 2 of chromosome 17. According to the human genome database and the review that was undertaken, the changes detected in this patient represent new mutations in the acid alpha-glucosidase gene, GAA. This claim is in agreement with the clinical features and biochemical changes found in the patient. CONCLUSION. A molecular genetic study is mandatory in patients suspected of having this disease.

Cell volume: Role in obesity and its maintenance minireview

Keeping volume within certain limits is a prerequisite for cell integrity and proper function. The defense against excess cell swelling is accomplished also by a reduction of the intracellular osmolarity by synthesis of osmotically less active macromolecules from their specific subunits (proteosynthesis and lipogenesis). At the same time proteolysis and lipolysis is inhibited. Conversely, cell shrinkage stimulates lipolysis, degradation of proteins to amino acids, degradation of glycogen to glucosephosphate and simultaneously protein, lipid and glycogen synthesis is inibited. The degradation products are osmotically more active than the macromolecules and their breakdown generates cellular osmolarity resulting in water entry into cells. Recently new interesting view of chronic changes of the cell volume and its role in model of body weight loss and regain in obesity is considered; secretion profile of adipocytes is related to their size. Decrease of body weight is constituted by the drop of fat in adipocytes, they consequently shrink. Surrounding extracellular matrix has to adjust to traction forces. To ascertain a sufficient supply of glucose and fat for re-storage, adipocytes change their pattern of secreted adipokines altering the total body metabolism and promoting energy intake. Shrunken adipocytes show insulin resistance, whereas glucose uptake is facilitated in osmotically swollen adipocytes. Compensating mechanism in patients on very-low calorie diet during weight maintenance period includes increase in water content of adipose tissue correlating with increase of insulin sensitivity. Consideration of participation these mechanisms might bring new insight into understanding of obesity pathophysiology and treatment.

Distinct disease phenotypes linked to different combinations of GAA mutations in a large late-onset GSDII sibship

BackgroundGlycogenosis type II (GSDII or Pompe disease) is an autosomal recessive disease, often characterized by a progressive accumulation of glycogen within lysosomes caused by a deficiency of α-1,4-glucosidase (GAA; acid maltase), a key enzyme of the glycogen degradation pathway. To date, more than 326 different mutations in the GAA gene have been identified in patients with GSDII but the course of the disease is difficult to be predicted on the basis of molecular genetic changes. Studies on large informative families are advisable to better define how genetics and non genetics factors like exercise and diet may influence the clinical phenotype.Methods and resultsIn this study, we report on clinical, instrumental, and pathological features as well as on molecular analysis of a family with 10 out of 13 siblings affected by late-onset Pompe disease. Three mutations segregated in the family, two of which are novel mutations. Siblings showing a more severe phenotype were compound heterozygous for c.118C > T [p.R40X] and c.2647-7G > A [p.N882fs] on GAA, whereas, two patients showing a mild phenotype were compound heterozygous c.2647-7G > A [p.N882fs] and c.2276G > C [p.G759A] mutations. Quantitative expression analysis showed, in the patients carrying p.R40X/ p.N882fs, a significant (p 0.01) correlation between the levels of expression of the mutated allele and the age at onset of the disease.ConclusionsAs far as we know, this is the largest informative family with late-onset Pompe disease described in the literature showing a peculiar complex set of mutations of GAA gene that may partially elucidate the clinical heterogeneity of this family.

Brain glycogenolysis, adrenoceptors, pyruvate carboxylase, Na(+),K(+)-ATPase and Marie E. Gibbs' pioneering learning studies.

The involvement of glycogenolysis, occurring in astrocytes but not in neurons, in learning is undisputed (Duran et al., 2013). According to one school of thought the role of astrocytes for learning is restricted to supply of substrate for neuronal oxidative metabolism. The present “perspective” suggests a more comprehensive and complex role, made possible by lack of glycogen degradation, unless specifically induced by either (1) activation of astrocytic receptors, perhaps especially β-adrenergic or (2) even small increases in extracellular K+ concentration above its normal resting level. It discusses (1) the known importance of glycogenolysis for glutamate formation, requiring pyruvate carboxylation; (2) the established role of K+-stimulated glycogenolysis for K+ uptake in cultured astrocytes, which probably indicates that astrocytes are an integral part of cellular K+ homeostasis in the brain in vivo; and (3) the plausible role of transmitter-induced glycogenolysis, stimulating Na+,K+-ATPase/NKCC1 activity and thereby contributing both to the post-excitatory undershoot in extracellular K+ concentration and the memory-enhancing effect of transmitter-mediated reduction of slow neuronal afterhyperpolarization (sAHP).

The effect of free nitrous acid on key anaerobic processes in enhanced biological phosphorus removal systems

In this study, the effect of nitrite/FNA on the anaerobic metabolism of polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) is investigated. The results clearly show that FNA has a detrimental effect on the acetate uptake rate by both PAOs and GAOs, but this adverse effect is much stronger on PAOs than on GAOs. Also, when FNA was increased, phosphate release to acetate uptake ratio by PAOs increased substantially (250–300% compared to control), which was accompanied by decreases (40–60%) in glycogen degradation and PHA production to VFA uptake. In contrast, these ratios for GAOs remained constant or increased slightly towards the highest FNA concentration applied. These results indicate that the anaerobic metabolism of PAOs is more adversely affected than that of GAOs when FNA is present. This might provide a competitive advantage to GAOs over PAOs in enhanced biological phosphorus removal systems when nitrite is present.

Glucose Utilization via Glycogen Phosphorylase Sustains Proliferation and Prevents Premature Senescence in Cancer Cells

Metabolic reprogramming of cancer cells provides energy and multiple intermediates critical for cell growth. Hypoxia in tumors represents a hostile environment that can encourage these transformations. We report that glycogen metabolism is upregulated in tumors invivo and in cancer cells invitro in response to hypoxia. Invitro, hypoxia induced an early accumulation of glycogen, followed bya gradual decline. Concordantly, glycogen synthase (GYS1) showed a rapid induction, followed by a later increase of glycogen phosphorylase (PYGL). PYGL depletion and the consequent glycogen accumulation led to increased reactive oxygen species (ROS) levels that contributed to a p53-dependent induction of senescence and markedly impaired tumorigenesis invivo. Metabolic analyses indicated that glycogen degradation by PYGL is important for the optimal function of the pentose phosphate pathway. Thus, glycogen metabolism is a key pathway induced by hypoxia, necessary for optimal glucose utilization, which represents a targetable mechanism of metabolic adaptation.

Effect of 1,5-Anhydro-D-Fructose on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes

1,5-Anhydro-D-fructose (1,5-AF) is a monosaccharide that shares a structural similarity to glucose. 1,5-AF is found in fungi, algae, Escherichia coli and rat liver and is produced by the degradation of starch and glycogen, which is catalyzed by the enzyme alpha-1,4-glucan lyase. However, the physiological role of 1,5-AF in mammalian tissues is not well understood. Here, we investigated the anti-obesity potential of 1,5-AF on adipogenesis in 3T3-L1 adipocytes. 1,5-AF caused a significant decrease in GPDH activity in 3T3-L1 preadipocytes and mature adipocytes without eliciting cytotoxicity, and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARgamma and C/EBPalpha. 1,5-AF also induced dose-dependent phosphorylation of AMP-activated protein kinase (AMPK), a cellular energy sensor. However, the total AMPK protein content remained unchanged. Furthermore, 1,5-AF increased the levels of reactive oxygen species, an important upstream signal for AMPK activation in 3T3-L1 adipocytes. Our results show that 1,5-AF exerts anti-obesity action in vitro and suggest that 1,5-AF is potentially a novel preventative agent for obesity and other metabolic diseases.

The chitin biosynthesis pathway in Entamoeba and the role of glucosamine-6-P isomerase by RNA interference

Entamoeba histolytica, the causative agent of amoebiasis, infects through its cyst form. A thick chitin wall protects the cyst from the harsh environment outside of the body. It is known that chitin is synthesized only during encystation, but the chitin synthesis pathway (CSP) of Entamoeba is not well characterized. In this report, we have identified the genes involved in chitin biosynthesis from the Entamoeba genome database and verified their expression profile at the transcriptional level in encysting Entamoeba invadens. Semi-quantitative RT-PCR (sqRT-PCR) analysis showed that all the chitin pathway genes are entirely absent or transcribed at low levels in trophozoites. The mRNA expression of most of the CSP genes reached their maximum level between 9 and 12h after the in vitro initiation of encystation. Double-stranded RNA-mediated silencing of glucosamine-6-P isomerase (Gln6Pi) reduced chitin synthesis to 62–64%, which indicates that Gln6Pi might be a key enzyme for regulating chitin synthesis in Entamoeba. The study of different enzymes involved in glycogen metabolism revealed that stored glycogen is converted to glucose during encystation. It is clear from the sqRT-PCR analysis that the rate of glycolysis decreases as encystation proceeds. Encystation up-regulates the expression of glycogen phosphorylase, which is responsible for glycogen degradation. The significant decrease in chitin synthesis in encysting cells treated with a specific inhibitor of glycogen phosphorylase indicates that the glucose obtained from the degradation of stored glycogen in trophozoites might be one of the major sources of glucose for chitin synthesis.

Bulbar muscle weakness and fatty lingual infiltration in glycogen storage disorder type IIIa

Glycogen storage disorder type III (GSD III) is a rare autosomal recessive disorder resulting from a deficiency of glycogen debranching enzyme, critical in cytosolic glycogen degradation. GSD IIIa, the most common form of GSD III, primarily affects the liver, cardiac muscle, and skeletal muscle. Although skeletal muscle weakness occurs commonly in GSD IIIa, bulbar muscle involvement has not been previously reported. Here we present three GSD IIIa patients with clinical evidence of bulbar weakness based on instrumental assessment of lingual strength. Dysarthria and/or dysphagia, generally mild in severity, were evident in all three individuals. One patient also underwent correlative magnetic resonance imaging (MRI) which was remarkable for fatty infiltration at the base of the intrinsic tongue musculature, as well as abnormal expansion of the fibro-fatty lingual septum. Additionally, we provide supportive evidence of diffuse glycogen infiltration of the tongue at necropsy in a naturally occurring canine model of GSD IIIa. While further investigation in a larger group of patients with GSD III is needed to determine the incidence of bulbar muscle involvement in this condition and whether it occurs in GSD IIIb, clinical surveillance of lingual strength is recommended.

Single fiber analyses of glycogen-related proteins reveal their differential association with glycogen in rat skeletal muscle

To understand how glycogen affects skeletal muscle physiology, we examined enzymes essential for muscle glycogen synthesis and degradation using single fibers from quiescent and stimulated rat skeletal muscle. Presenting a shift in paradigm, we show these proteins are differentially associated with glycogen granules. Protein diffusibility and/or abundance of glycogenin, glycogen branching enzyme (GBE), debranching enzyme (GDE), phosphorylase (GP), and synthase (GS) were examined in fibers isolated from rat fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscle. GDE and GP proteins were more abundant (~10- to 100-fold) in fibers from EDL compared with SOL muscle. GS and glycogenin proteins were similar between muscles while GBE had an approximately fourfold greater abundance in SOL muscle. Mechanically skinned fibers exposed to physiological buffer for 10 min showed ~70% total pools of GBE and GP were diffusible (nonbound), whereas GDE and GS were considerably less diffusible. Intense in vitro stimulation, sufficient to elicit a ~50% decrease in intracellular glycogen, increased diffusibility of GDE, GP, and GS (~15-60%) and decreased GBE diffusibility (~20%). Amylase treatment, which breaks α-1,4 linkages of glycogen, indicated differential diffusibilities and hence glycogen associations of GDE and GS. Membrane solubilization (1% Triton-X-100) allowed a small additional amount of GDE and GS to diffuse from fibers, suggesting the majority of nonglycogen-associated GDE/GS is associated with myofibrillar/contractile network of muscle rather than membranes. Given differences in enzymes required for glycogen metabolism, the current findings suggest glycogen particles have fiber-type-dependent structures. The greater catabolic potential of glycogen breakdown in fast-twitch fibers may account for different contraction induced rates of glycogen utilization.

Effects of lairage time on welfare indicators, energy metabolism and meat quality of pigs in Beijing

A total of forty Duroc–Landrace–Large White female pigs (90±5kg) were used to study the effects of different lairage times (0h, 3h, 8h, 24h) on welfare, energy metabolism and meat quality. The results showed that lairage time of 3h led to a lower blood cortisol, a decreased drip loss and a delayed degradation of glycogen in muscles compared with pigs without rest, while lairage times of 8h and 24h resulted in a significant increase in pork toughness. It was concluded that three hours of lairage was appropriate to reduce pre-slaughter stress and obtain better meat quality for pigs transported for 4h in winter, under the most frequent commercial conditions in Beijing, China. No lairage, or excessively long lairage time, might compromise animal welfare and meat quality.

Vital staining with iodine solution in oral cancer: iodine infiltration, cell proliferation, and glucose transporter 1

Vital staining with iodine solution has been used to distinguish dysplastic/malignant oral epithelium from normal mucosa. However, little is known about its critical mechanism. The purpose of this study was to visualize how iodine infiltrates the oral epithelium and reacts with glycogen. In addition, we tested the hypothesis that higher cell proliferation requires increased energy consumption, and consequently exhausted glycogen may lead to a failure to be stained by iodine solution. Fifteen frozen tissue samples of iodine-stained and -unstained mucosa were obtained from 15 cases of oral squamous cell carcinoma (OSCC). Serial frozen sections were cut and examined with hematoxylin and eosin and periodic acid-Schiff methods and immunohistochemical staining for p53, Ki67 and glucose transporter 1 (GLUT 1). Iodine solution was able to penetrate normal epithelium to a maximum depth neighboring the parabasal layer, but iodine-stained areas were completely consistent with glycogen distribution only in the upper superficial layer. Iodine-negative epithelium presented significantly higher immunoreactions for P53 and GLUT 1 in basal, parabasal, and superficial layers, respectively, whereas the reaction for Ki67 in the superficial layer was higher than that in iodine-positive epithelium (Wilcoxon signed-rank test, P < 0.05). Iodine infiltrated and reacted with glycogen mainly in the upper superficial layer of the nonkeratinized epithelium. Both histological and molecular margins can be confirmed by iodine vital staining in OSCC. It is also suggested that high cell proliferation induced elevated glycolysis, resulting in an intraepithelial glycogen degradation and consequent failure to be stained by iodine solution.

GLUT4 is not essential for exercise-induced exaggerated muscle glycogen degradation in AMPKα2 knockout mice

The purpose of this study was to explore the effects of AMPKα2 knockout on expression of GLUT4 after exercise with different intensities. This was investigated in the quadriceps femoris muscle from control, lower intensity (12m/minute) and higher intensity (20m/minute) running groups of wild-type (WT) and AMPKα2 knockout (KO) mice. The skeletal muscle glycogen content was also measured to investigate the role of AMPK in regulation of glycogen metabolism. GLUT4 mRNA was increased immediately at the end of 60minutes of running, but there were no differences between WT and KO mice, and between lower intensity and higher intensity groups. Pre-exercise muscle glycogen levels were not different between WT and KO; however, the lack of the α2-isoform was associated with a generally lower level of muscle glycogen after 60minutes of running either with lower intensity or higher intensity. The finding that KO of the AMPKα2 isoform had no effect on expressions of GLUT4 mRNA and protein expression in mouse skeletal muscle and that muscle glycogen degradation was greater in AMPKα2 KO mice than that in WT mice after different intensity exercises, provides further evidence that AMPK is dispensable in exercise-induced expression of GLUT4, and suggests alternative pathways other than GLUT4 being involved in the regulation of muscle glycogen degradation by AMPK. Also, the present investigation demonstrated that higher intensity (20m/minute) treadmill running, lasting 1h, increased GLUT4 mRNA in mice skeletal muscle to a level similar to that attained after 1h of lower intensity (12m/minute) treadmill running.

Luis Federico Leloir, or how to do good science in a hostile environment

Luis Federico Leloir, or how to do good science in a hostile environment

Phosphoglucomutase (PGM 1) Deficiency: A Novel Defect of Muscle Glycogen Degradation and Synthesis (P07.200)

Objective: Evaluate the cause of exertional muscle fatigue, contractures and rhabdomyolysis in a young woman. Background An 18 year old woman reported lifelong fatigue with modest exercise and episodes of muscle contractures, pain and swelling with marked elevations in serum creatine kinase levels after more vigorous exercise. Design/Methods: Forearm and cycle exercise, muscle glycogen determinations, and relevant enzymatic and genetic evaluation were performed. Results: Ischemic forearm exercise resulted in no increase in lactate, an exaggerated increase in ammonia, rapid contractile fatigue and a finger flexor muscle contracture. Cycle exercise revealed low oxidative capacity and a spontaneous second wind, associated with a 40 beat per minute (bpm) drop in exercise heart rate, from 159 (between minute 5-6) to 119 bpm at minute 14 of sustained exercise with a corresponding fall in perceived exertion, thus mirroring the response heretofore considered diagnostic of McArdle disease. However enzymatic activity of muscle phosphorylase and other known defects of muscle glycogenolysis were within normal limits and muscle glycogen levels were low normal as assessed biochemically (controls = 1.1±0.2%; patient = 0.7%) and with 13-C MRS in contrast to McArdle disease (2.5±0.4 %). Evaluation of other glycolytic enzymes revealed a complete absence of muscle phosphoglucomutase (PGM1) activity, the enzyme that catalyzes the conversion of phosphorylase-derived glucose-1-phosphate to glucose-6-phosphate for metabolism via glycolysis and the reverse reaction for glycogen synthesis from glucose. Genetic analysis revealed that the patient was a compound heterozygote for a nonsense mutation (Q530X in exon 10) and a missense mutation (R422W) in exon 8 of PGM1. Conclusions: This patient has a novel defect in phosphoglucomutase (PGM1) that mimics the clinical and physiological features of impaired muscle glycogenolysis due to muscle phosphorylase deficiency (McArdle disease). The finding of blocked muscle glycogenolysis in combination with low muscle glycogen implies that this enzymatic defect impairs both glycogen degradation and synthesis. Supported by: The Muscular Dystrophy Association and The Giant Tiger Foundation. Disclosure: Dr. Haller has nothing to disclose. Dr. Heinicke has nothing to disclose. Dr. Newby has nothing to disclose. Dr. Wyrick has nothing to disclose. Dr. Dimitrov has nothing to disclose. Dr. Mancias has nothing to disclose. Dr. Cohen has nothing to disclose.

ACSL1 multi‐tissue knockout mice are resistant to diet‐and age‐induced obesity and insulin resistance

Long chain acyl‐CoA synthetase 1 (ACSL1) is the major activator of long‐chain fatty acids in heart and adipose tissue. In order to understand the functional role of ACSL1, we studied mice with a temporally‐induced knockout of ACSL1 in multiple tissues (Acsl1T−/−), including heart, skeletal muscle, kidney, and white adipose. Compared to littermate controls (tamoxifen‐injected ACSL1flox/flox), lack of ACSL1 caused 80–90% lower oxidation of palmitate in heart and adipose. Compared to controls, hearts that lacked ACSL1 took up 75% less [1‐14C]bromopalmitate and 10‐fold more 2‐[14C]deoxyglucose. Compared to controls, chow‐fed Acsl1T−/− mice had higher rates of glycogen degradation in liver and heart. When fed a high fat diet (HFD; 45% of kcal from lard and soybean oil), ACSL1T−/− male mice failed to become obese. HFD‐fed ACSL1T−/− and control mice had similar food intake, respiratory quotients and heat production, but ACSL1T−/− mice were significantly more active at night. HFD‐fed control mice had abnormal glucose and insulin tolerance tests, whereas HFD‐fed ACSL1T−/− mice maintained normal whole‐body insulin sensitivity. With aging, 14‐month old chow‐fed ACSL1T−/− female mice also had a lower fat mass and better glucose tolerance than controls. Thus, ACSL1T−/− mice were protected from HFD‐and age‐induced obesity and insulin resistance.

Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) has several significant characteristics based on molecular features that are distinct from those of ovarian high-grade serous carcinoma. Cellular glycogen accumulation is the most conspicuous feature of OCCC and in the present study its metabolic mechanism was investigated. The amount of glycogen in cells cultured under hypoxia increased significantly and approximately doubled after 48 h (P<0.01) compared to that under normoxic conditions. Periodic acid-Schiff positive staining also demonstrated intracellular glycogen storage. Western blot analysis revealed that HIF1α, which was overexpressed and stabilized under hypoxic conditions, led to an increase in the levels of cellular glycogen synthase 1, muscle type (GYS1), and conversely to a decrease in inactive phosphorylated GYS1 at serine (Ser) 641. Additional increases were observed in both protein phosphatase 1, which dephosphorylates and thereby induces GYS1 enzyme activity, and glycogen synthase kinase 3 beta (GSK3β) phosphorylated at Ser9, which is inactive on phosphorylation of GYS1 and subsequently induces its enzyme activity. By contrast, the level of PYGM-b decreased. These results indicated that the glycogen accumulation under a hypoxic environment resulted in the promotion of glycogen synthesis, but did not lead to inhibition of glycogen degradation and/or consumption. Under hypoxic conditions, HAC2 cells showed activation of the PI3K/AKT pathway caused by a mutation in exon 20 of PIK3CA, encoding the catalytic subunit p110α of PI3K. The resulting activation of AKT (phosphoSer473) also plays a role as a central enhancer in glycogen synthesis through suppression of GSK3β via phosphorylation at Ser9. Hypoxia decreased the cytocidal activity of cisplatin and doxorubicin to various degrees. In conclusion, the hypoxic conditions together with HIF1 expression and stabilization increased the intracellular glycogen contents and resistance to the anticancer drugs.

Beta2-Adrenergic Receptor and Astrocyte Glucose Metabolism

Astrocyte glucose metabolism functions to maintain brain activity in both normal and stress conditions. Dysregulation of astrocyte glucose metabolism relates to development of neuronal disease, such as multiple sclerosis and Alzheimer's disease. In response to acute stress, beta2-adrenergic receptor is activated and initiates multiple signaling events mediated by Gs, Gi, arrestin, or other effectors depending on specific cellular contexts. In astrocytes, beta2-adrenergic receptor promotes glucose uptake through GLUT1 and accelerates glycogen degradation via coupling to Gs and second messenger cAMP-dependent pathway. Beta2-adrenergic receptor may regulate other steps in astrocyte glucose metabolism, such as lactate production or transduction. Inappropriate regulation of beta2-adrenergic receptor activity can disrupt normal glucose metabolism, and leads to accelerate neuronal disease development. It was demonstrated that the absence of beta2-adrenergic receptor in astrocytes occurred in multiple sclerosis patients, and the increased beta2-adrenergic receptor activity relates to Alzheimer's disease. A clear view of beta2-adrenergic receptor-mediated signaling pathways in regulating astrocyte glucose metabolism could help us to develop neuronal diseases treatment by targeting to the beta2-adrenergic receptor.

Review on the Microbiological and Biochemistrial Characters of Enhanced Biological Phosphorus Removal System*

The microbiological and biochemical characteristics of enhanced biological phosphorus removal (EBPR) process was summarized. With respect to the microbiology, the competition and relationship among the main microbes in the system, including poly-phosphate accumulating organisms (PAOs), glycogen accumulating organisms (GAOs) and denitrified PAOs (DPAOs) were concluded. A wide variety of PAOs were separated from the EBPR system and the Accumulibacter was considered a typical PAO, existing in all kinds of EBPR systems. There was still controversy concerning the relationship between PAOs and GAOs and the classification of DPAOs. With respect to the biochemistry, the relevance between the intracellular polymers and the metabolic function was concluded. The reducing power in the anaerobic phase was provided both by the TCA circulation and the glycolysis process, influenced by the population structure and experiment condition. The degradation of glycogen was different when the bacterial strain was different and the glycogen was the regulator of the redox equilibrium in the cell. The composition of poly-β-hydroxyalkanoates (PH As) was determined by the organic substrate, and when propionic acid was the substrate, four monomers of PHAs could be detected. The power used in the anaerobic P-releasing was derived from the decomposition of polyphosphate and glycogen, while the amount of power needed was influenced by experiment condition.