Glycogen and Enzymes of Glycogen Metabolism in Rat Embryos and Fetal Organs

Gutiérrez-Correa, José; Hod, Moshe; Passoneau, Janet V.; Freinkel, Norbert

doi:10.1159/000243363

Cited by 15 publications

(15 citation statements)

References 14 publications

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“…In the developing lung, the glycogen level is low early in gestation and high from midgestation until term, when it declines (7,14,15). Liver glycogen is present at a low level until late gestation (7,14,15,25), consistent with a role in providing glucose for the newborn prior to the development by the liver of the capacity to produce glucose by gluconeogenesis (22). The concentration of fetal skeletal muscle glycogen has already reached the adult level when glycogen accumulation is just beginning in the liver.…”

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confidence: 98%

“…Relatively low levels of glycogen are present in fertilized mouse eggs (38); however, there is evidence of high glycogen synthase activity in one-cell mouse embryos (8), and by the two-cell stage, significant glycogen accumulation can be measured (39). Several tissues from a variety of mammals have been analyzed for the appearance of glycogen and glycogen synthase activity in later stages of embryonic development (7,15,25). In the developing lung, the glycogen level is low early in gestation and high from midgestation until term, when it declines (7,14,15).…”

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confidence: 99%

“…By late gestation, the level of muscle glycogen is higher than that in adult muscle (15). Cardiac glycogen is present at high levels during early to midgestation before falling to low levels at the time of birth (7,14,15,25). The facts that glycogen is present and that its level changes during the embryonic development of several tissues suggest that it may have a specific role, but few studies have provided definitive evidence regarding this point.…”

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confidence: 99%

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Abnormal Cardiac Development in the Absence of Heart Glycogen

Pederson

Chen²,

Schroeder

et al. 2004

Molecular and Cellular Biology

105

113

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Glycogen serves as a repository of glucose in many mammalian tissues. Mice lacking this glucose reserve in muscle, heart, and several other tissues were generated by disruption of the GYS1 gene, which encodes an isoform of glycogen synthase. Crossing mice heterozygous for the GYS1 disruption resulted in a significant underrepresentation of GYS1-null mice in the offspring. Timed matings established that Mendelian inheritance was followed for up to 18.5 days postcoitum (dpc) and that ϳ90% of GYS1-null animals died soon after birth due to impaired cardiac function. Defects in cardiac development began between 11.5 and 14.5 dpc. At 18.5 dpc, the hearts were significantly smaller, with reduced ventricular chamber size and enlarged atria. Consistent with impaired cardiac function, edema, pooling of blood, and hemorrhagic liver were seen. Glycogen synthase and glycogen were undetectable in cardiac muscle and skeletal muscle from the surviving null mice, and the hearts showed normal morphology and function. Congenital heart disease is one of the most common birth defects in humans, at up to 1 in 50 live births. The results provide the first direct evidence that the ability to synthesize glycogen in cardiac muscle is critical for normal heart development and hence that its impairment could be a significant contributor to congenital heart defects.

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confidence: 98%

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confidence: 99%

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confidence: 99%

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Abnormal Cardiac Development in the Absence of Heart Glycogen

Pederson

Chen²,

Schroeder

et al. 2004

Molecular and Cellular Biology

105

113

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“…Glycogen is 10-to 20-fold more concentrated than in the adult heart, and when oxygen and glucose are lacking it represents an important source of glucose to maintain the production of glycolytically derived ATP with high, intermediate, and low glycogenolytic capacities in the atria (A), ventricle (V), and outflow tract (OT), respectively (42). The fact that glycogen synthase (GS) activity is specially high in the embryonic/fetal heart, accounting for the important glycogen stores (14), prompted us to investigate the role that ADO signaling could play in regulation of GS and glycogen content. Furthermore, to what extent a prolonged hypoxia during embryogenesis alters expression of the enzymes, transporters, and receptors of the adenosinergic system within the developing heart and affects its tolerance to a subsequent episode of anoxia/reoxygenation were examined.…”

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confidence: 99%

A hypoxic episode during cardiogenesis downregulates the adenosinergic system and alters the myocardial anoxic tolerance

Robin

Marcillac

Raddatz

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Robin E, Marcillac F, Raddatz E. A hypoxic episode during cardiogenesis downregulates the adenosinergic system and alters the myocardial anoxic tolerance. Am J Physiol Regul Integr Comp Physiol 308: R614 -R626, 2015. First published January 28, 2015 doi:10.1152/ajpregu.00423.2014.-To what extent hypoxia alters the adenosine (ADO) system and impacts on cardiac function during embryogenesis is not known. Ectonucleoside triphosphate diphosphohydrolase (CD39), ecto-5=-nucleotidase (CD73), adenosine kinase (AdK), adenosine deaminase (ADA), equilibrative (ENT1,3,4), and concentrative (CNT3) transporters and ADO receptors A 1, A2A, A2B, and A3 constitute the adenosinergic system. During the first 4 days of development chick embryos were exposed in ovo to normoxia followed or not followed by 6 h hypoxia. ADO and glycogen content and mRNA expression of the genes were determined in the atria, ventricle, and outflow tract of the normoxic (N) and hypoxic (H) hearts. Electrocardiogram and ventricular shortening of the N and H hearts were recorded ex vivo throughout anoxia/reoxygenation Ϯ ADO. Under basal conditions, CD39, CD73, ADK, ADA, ENT1,3,4, CNT3, and ADO receptors were differentially expressed in the atria, ventricle, and outflow tract. In H hearts ADO level doubled, glycogen decreased, and mRNA expression of all the investigated genes was downregulated by hypoxia, except for A 2A and A3 receptors. The most rapid and marked downregulation was found for ADA in atria. H hearts were arrhythmic and more vulnerable to anoxia-reoxygenation than N hearts. Despite downregulation of the genes, exposure of isolated hearts to ADO 1) preserved glycogen through activation of A1 receptor and Akt-GSK3␤-GS pathway, 2) prolonged activity and improved conduction under anoxia, and 3) restored QT interval in H hearts. Thus hypoxia-induced downregulation of the adenosinergic system can be regarded as a coping response, limiting the detrimental accumulation of ADO without interfering with ADO signaling.anoxia-reoxygenation; arrhythmias; glycogen metabolism; hypoxia; adenosine signaling LOW OXYGEN LEVEL is a prerequisite for normal embryonic and fetal growth including the cardiovascular system. However, hypoxia-induced imbalance between O 2 supply and demand impacts gene expression, metabolism, growth, and function (13,17,20,21,33,45,48,50,53,56). Oxygen deprivation during critical periods of embryogenesis impairs heart development and function with hemodynamic disturbances resulting in fetal growth retardation and increasing the risk of cardiovascular disease in adulthood, the so-called "fetal programming" (8,12,26,38,47,57,59). Maternal hypoxemia, reduction in umbilical blood flow, or placental insufficiency can rapidly lead to acute or chronic ischemia and/or hypoxia, which exacerbates ATP-derived adenosine (ADO) production. Since ADO represents an important regulator of the embryonic cardiovascular function (35), the present study focuses on the modulation of the adenosinergic system by hypoxia and its functional consequences in the d...

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“…At midgestation, hepatoblasts surrounding the portal vein differentiate into biliary epithelial cells expressing cytokeratin 19 (CK19) (30 -33). During late gestation and perinatal stages, hepatoblasts differentiate into hepatocytes, which produce a number of metabolic enzymes, including carbamoylphosphate synthetase I, glucose-6-phosphatase (G6Pase), tyrosine aminotransferase (TAT) and glycogen synthase (Gys) (5,7,8,11,24,25).…”

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confidence: 99%

New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts

Miki¹,

Tatsumi²,

Matsumoto³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatoblasts have the potential to differentiate into both hepatocytes and biliary epithelial cells through a differentiation program that has not been fully elucidated. With the aim to better define the mechanism of differentiation of hepatoblasts, we isolated hepatoblasts and established new culture systems. We isolated hepatoblasts from E12.5 fetal mouse liver by using E-cadherin. The E-cadherin+ cells expressed α-fetoprotein (AFP) and albumin (Alb) but not cytokeratin 19 (CK19). Transplantation of the E-cadherin+ cells into mice that had been subjected to liver injury or biliary epithelial injury led to differentiation of the cells into hepatocytes or biliary epithelial cells, respectively. In a low-cell-density culture system in the absence of additional growth factors, E-cadherin+ cells formed colonies of various sizes, largely comprising Alb-positive cells. Supplementation of the culture medium with hepatocyte growth factor and epidermal growth factor promoted proliferation of the cells. Thus the low-cell-density culture system should be useful to identify inductive factors that regulate the proliferation and differentiation of hepatoblasts. In a high-cell-density system in the presence of oncostatin M+dexamethasone, E14.5, but not E12.5, E-cadherin+ cells differentiated into mature hepatocytes, suggesting that unidentified factors are involved in hepatic maturation. Culture of E-cadherin+ cells derived from E12.5 or E14.5 liver under high-cell-density conditions should allow elucidation of the mechanism of hepatic differentiation in greater detail. These new culture systems should be of use to identify growth factors that induce hepatoblasts to proliferate or differentiate into hepatocytes and biliary epithelial cells.

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Glycogen and Enzymes of Glycogen Metabolism in Rat Embryos and Fetal Organs

Cited by 15 publications

References 14 publications

Abnormal Cardiac Development in the Absence of Heart Glycogen

Abnormal Cardiac Development in the Absence of Heart Glycogen

A hypoxic episode during cardiogenesis downregulates the adenosinergic system and alters the myocardial anoxic tolerance

New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts

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