A Study of the Neurohumoral Control of Glycolysis in the Mouse Brain in vivo: Role of Noradrenaline and Dopamine

1975 ◽  
Vol 30 (5-6) ◽  
pp. 385-391 ◽  
Author(s):  
B. E. Leonard
Keyword(s):  
Mouse Brain ◽  
Sodium Fluoride ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Adenyl Cyclase ◽  
Membrane Bound ◽  
Adenyl Cyclase System ◽  
Neurohumoral Control

Abstract Noradrenaline, Dopamine, Glycolysis, Adenyl Cyclase Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of “free” glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with α-methyl-p-tyrosine. ʟᴅ-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or monophosphate on glycolysis.

scholarly journals Xenon and Sevoflurane Protect against Brain Injury in a Neonatal Asphyxia Model

2008 ◽  
Vol 109 (5) ◽  
pp. 782-789 ◽  
Author(s):  
Yan Luo ◽  
Daqing Ma ◽  
Edmund Ieong ◽  
Robert D. Sanders ◽  
Buwei Yu ◽  
...  
Keyword(s):  
Infarct Size ◽  
Cyclic Adenosine Monophosphate ◽  
Glucose Deprivation ◽  
Adenosine Monophosphate ◽  
Oxygen Glucose Deprivation ◽  
Response Element ◽  
Element Binding Protein ◽  
Phosphoinositide 3 Kinase

Background Perinatal hypoxia-ischemia causes significant morbidity and mortality. Xenon and sevoflurane may be used as inhalational analgesics for labor. Therefore, the authors investigated the potential application of these agents independently and in combination to attenuate perinatal injury. Methods Oxygen-glucose deprivation injury was induced in pure neuronal or neuronal-glial cocultures 24 h after preconditioning with xenon and/or sevoflurane. Cell death was assessed by lactate dehydrogenase release or staining with annexin V-propidium iodide. The mediating role of phosphoinositide-3-kinase signaling in putative protection was assessed using wortmannin, its cognate antagonist. In separate in vivo experiments, perinatal asphyxia was induced 4 hours after preconditioning with analgesic doses alone and in combination; infarct size was assessed 7 days later, and neuromotor function was evaluated at 30 days in separate cohorts. The role of phosphorylated cyclic adenosine monophosphate response element binding protein in the preconditioning was assessed by immunoblotting. Results Both anesthetics preconditioned against oxygen-glucose deprivation in vitro alone and in combination. The combination increased cellular viability via phosphoinositide-3- kinase signaling. In in vivo studies, xenon (75%) and sevoflurane (1.5%) alone as well as in combination (20% xenon and 0.75% sevoflurane) reduced infarct size in a model of neonatal asphyxia. Preconditioning with xenon and the combination of xenon and sevoflurane resulted in long-term functional neuroprotection associated with enhanced phosphorylated cyclic adenosine monophosphate response element binding protein signaling. Conclusions Preconditioning with xenon and sevoflurane provided long-lasting neuroprotection in a perinatal hypoxic-ischemic model and may represent a viable method to preempt neuronal injury after an unpredictable asphyxial event in the perinatal period.

EFFECT OF IODIDE ON THE ADENYL CYCLASE SYSTEM OF THE MOUSE THYROID IN VIVO

1978 ◽  
Vol 88 (3) ◽  
pp. 517-527 ◽  
Author(s):  
C. Saddok ◽  
M. Gafni ◽  
J. Gross
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Iodine Content ◽  
Adenosine Monophosphate ◽  
Iodine Intake ◽  
Adenyl Cyclase ◽  
Camp Accumulation ◽  
Adenyl Cyclase Activity ◽  
Pre Treatment ◽  
Highly Correlated

ABSTRACT Iodide, administered to mice either acutely or chronically, depressed the thyroidal cyclic adenosine monophosphate (cAMP) response to 20 mU bovine TSH. When iodide was administered acutely there was a 60% reduction in the cAMP accumulation after 100 μg, or 1 μg KI given to mice on normal iodine diet (NID), or low iodine diet (LID), respectively. When iodide was administered chronically by supplementing the LID with graded doses of KI for 11 days, the cAMP response to TSH was found to be inversely related to the dietary iodine. Inhibition occurred after 5 μg KI, a dose similar to the daily iodine intake. Iodide depressed, but did not abolish, the thyroidal cAMP response to TSH. Iodide had no effect on phosphodiesterase activity, whereas thyroidal adenyl cyclase activity was diminished by the prior administration of 100 μg KI. The iodide effect was abolished by pre-treatment with methylmercaptoimidazole i.e. the inhibition is related to iodide oxidation. The newly organified thyroidal iodine (NOTI), formed at 2 h from 0.1–1000 μg KI was determined. The amount of NOTI was highly correlated to the degree of inhibition, irrespective of the iodine content of the diet. This relationship was continuous up to 100 ng NOTI and 70% inhibition, which are the maximal values obtained for NOTI formation and inhibition of cAMP accumulation. These plateau levels were reached with 100 or 1 μg KI in mice on NID or LID, respectively. These results indicate that the inhibitor is an iodinated substance whose intrathyroidal formation is quantitatively parallel to, or a part of NOTI.

scholarly journals The Effect of Norepinephrine and Dibutyryl Cyclic Adenosine Monophosphate on Cation Transport in Duck Erythrocytes

1971 ◽  
Vol 57 (6) ◽  
pp. 752-766 ◽  
Author(s):  
D. H. Riddick ◽  
F. M. Kregenow ◽  
J. Orloff
Keyword(s):  
Steady State ◽  
Synthetic Medium ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Blocking Agent ◽  
Steady State Levels ◽  
Membrane Bound ◽  
Adenyl Cyclase System ◽  
Adrenergic Blocking ◽  
Analogous Effect

Freshly prepared duck erythrocytes, incubated either in plasma or an isotonic synthetic medium containing norepinephrine ([K] of both media ∼ 2.5 mM), maintain water and electrolyte composition in the steady state (upper steady state) for at least 90 min. If incubated in the synthetic medium without norepinephrine or in plasma to which a ß-adrenergic blocking agent (propranolol) is added, the cells lose both water and electrolyte (predominantly KCl) until a new steady state is reached (lower steady state). Reaccumulation of water and electrolyte from isotonic solutions toward the upper steady-state levels requires the addition of norepinephrine and KCl. Reaccumulation is maximal when the concentration of K and norepinephrine in the medium is 15 mM and 10-7 M, respectively. Dibutyryl cyclic-AMP (10-2 M) mimics norepinephrine in lower steady-state cells. Although an analogous effect in upper steady-state cells was not established with certainty, it is proposed that the catecholamine-induced net changes in water and electrolyte movement in duck erythrocytes are a consequence of stimulation of the activity of a membrane-bound adenyl cyclase system.

scholarly journals CHEMISTRY OF THE FILAMENTS AND TUBULES OF BRAIN

1973 ◽  
Vol 21 (6) ◽  
pp. 529-539 ◽  
Author(s):  
MICHAEL L. SHELANSKI
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biochemical Properties ◽  
Microtubule Assembly ◽  
Protein Subunit ◽  
Tentative Model ◽  
In Vitro Assembly

In this paper the main fibrous proteins of the nervous system are discussed from a biochemical standpoint. The biochemical properties of the proteins making up the neurofilaments and neurotubules are briefly reviewed and attention is turned to the assembly of supramolecular structures from tubulin, the microtubular protein. Vinblastine-induced assembly is surveyed as a model for assembly and the role of guanosine 5'-triphosphate in this is noted. The in vitro assembly conditions for microtubules recently introduced by Weisenberg are recounted and the role of calcium in controlling this is noted. The role of guanosine 5'-triphosphate and the roles it may and may not play are discussed in some detail as is the role of cyclic adenosine monophosphate. The evidence presented does not support a role for phosphorylation of the protein subunit in microtubule assembly A tentative model for the in vivo control of microtubule assembly and the possible relation of cyclic adenosine monophosphate and hormones such as insulin and nerve growth factor are presented.

scholarly journals HISTOCHEMICAL LOCALIZATION OF ADENYL CYCLASE IN THE FUNGUS PHYCOMYCES BLAKESLEEANUS

1973 ◽  
Vol 21 (12) ◽  
pp. 1041-1046 ◽  
Author(s):  
J. C. TU ◽  
S. K. MALHOTRA
Keyword(s):  
Plasma Membrane ◽  
Sodium Fluoride ◽  
Stage Iv ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Adenyl Cyclase ◽  
Mitochondrial Membranes ◽  
Phycomyces Blakesleeanus ◽  
Nuclear Membranes

The presence of adenyl cyclase in Phycomyces blakesleeanus has been investigated in situ histochemically by lead precipitation of pyrophosphate liberated by conversion of adenosine triphosphate to cyclic adenosine monophosphate. Dormant spores, heat-shocked spores, germinating spores and the growing zone of sporangiophore (stage IV) of the fungus were studied. Electron-dense lead precipitate was localized in association with plasma membrane and between the mitochondrial membranes and nuclear membranes in all stages investigated. This reaction product is not inhibited by sodium fluoride, and adenyl cyclase is the only known enzyme stimulated by sodium fluoride. Comparable studies on the hepatocytes of mouse liver showed the reaction product in association with plasma membrane only.

Mechanisms of ATP to cAMP Conversion Catalyzed by the Mammalian Adenylyl Cyclase: A Role of Magnesium Coordination Shells and Proton Wires

2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin
Keyword(s):  
Adenylyl Cyclase ◽  
Bond Cleavage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Md Simulations ◽  
Coordination Shell ◽  
Energy Profile ◽  
One Step ◽  
Type V

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>

scholarly journals Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

2021 ◽  
Vol 22 (14) ◽  
pp. 7256
Author(s):  
Vianet Argelia Tello-Flores ◽  
Fredy Omar Beltrán-Anaya ◽  
Marco Antonio Ramírez-Vargas ◽  
Brenda Ely Esteban-Casales ◽  
Napoleón Navarro-Tito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Species ◽  
Necrosis Factor Alpha ◽  
Polypyrimidine Tract Binding Protein ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

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