scholarly journals Guanosine modulates SUMO2/3-ylation in neurons and astrocytes via adenosine receptors

2020 ◽  
Vol 16 (3) ◽  
pp. 439-450
Author(s):  
Camila A. Zanella ◽  
Carla I. Tasca ◽  
Jeremy M. Henley ◽  
Kevin A. Wilkinson ◽  
Helena I. Cimarosti
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Attractive Potential ◽  
Receptor Interaction ◽  
Post Translational Modification ◽  
Neuroprotective Effects ◽  
Adenosine Receptor Antagonist ◽  
Wide Range

Abstract SUMOylation is a post-translational modification (PTM) whereby members of the Small Ubiquitin-like MOdifier (SUMO) family of proteins are conjugated to lysine residues in target proteins. SUMOylation has been implicated in a wide range of physiological and pathological processes, and much attention has been given to its role in neurodegenerative conditions. Due to its reported role in neuroprotection, pharmacological modulation of SUMOylation represents an attractive potential therapeutic strategy in a number of different brain disorders. However, very few compounds that target the SUMOylation pathway have been identified. Guanosine is an endogenous nucleoside with important neuromodulatory and neuroprotective effects. Experimental evidence has shown that guanosine can modulate different intracellular pathways, including PTMs. In the present study we examined whether guanosine alters global protein SUMOylation. Primary cortical neurons and astrocytes were treated with guanosine at 1, 10, 100, 300, or 500 μM at four time points, 1, 6, 24, or 48 h. We show that guanosine increases global SUMO2/3-ylation in neurons and astrocytes at 1 h at concentrations above 10 μM. The molecular mechanisms involved in this effect were evaluated in neurons. The guanosine-induced increase in global SUMO2/3-ylation was still observed in the presence of dipyridamole, which prevents guanosine internalization, demonstrating an extracellular guanosine-induced effect. Furthermore, the A1 adenosine receptor antagonist DPCPX abolished the guanosine-induced increase in SUMO2/3-ylation. The A2A adenosine receptor antagonist ZM241385 increased SUMOylation per se, but did not alter guanosine-induced SUMOylation, suggesting that guanosine may modulate SUMO2/3-ylation through an A1-A2A receptor interaction. Taken together, this is the first report to show guanosine as a SUMO2/3-ylation enhancer in astrocytes and neurons.

scholarly journals 3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A2A-Mediated Neuroprotective Effects

2011 ◽  
Vol 2 (9) ◽  
pp. 526-535 ◽  
Author(s):  
Alessia Scatena ◽  
Francesco Fornai ◽  
Maria Letizia Trincavelli ◽  
Sabrina Taliani ◽  
Simona Daniele ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Neuroprotective Effects ◽  
Adenosine Receptor Antagonist

CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells

1995 ◽  
Vol 269 (1) ◽  
pp. C226-C233 ◽  
Author(s):  
V. Casavola ◽  
R. J. Turner ◽  
C. Guay-Broder ◽  
K. A. Jacobson ◽  
O. Eidelman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Receptor Antagonist ◽  
Intracellular Ph ◽  
Adenosine Receptor ◽  
Ph Regulation ◽  
Cystic Fibrosis Transmembrane Regulator ◽  
Wild Type ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist ◽  
Cystic Fibrosis Transmembrane

The selective A1-adenosine-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), has been reported to activate Cl- efflux from cystic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bearing the cystic fibrosis transmembrane regulator(delta F508) mutation, but has little effect on the same process in cells repaired by transfection with wild-type cystic fibrosis transmembrane regulator (O. Eidelman, C. Guay-Broder, P. J. M. van Galen, K. A. Jacobson, C. Fox, R. J. Turner, Z. I. Cabantchik, and H. B. Pollard. Proc. Natl. Acad. Sci. USA 89: 5562-5566, 1992). We report here that CPX downregulates Na+/H+ exchange activity in CFPAC-1 cells but has a much smaller effect on cells repaired with the wild-type gene. CPX also mildly decreases resting intracellular pH. In CFPAC-1 cells, this downregulation is dependent on the presence of adenosine, since pretreatment of the cells with adenosine deaminase blocks the CPX effect. We also show that, by contrast, CPX action on these cells does not lead to alterations in intracellular free Ca2+ concentration. We conclude that CPX affects pH regulation in CFPAC-1 cells, probably by antagonizing the tonic action of endogenous adenosine.

Synthesis of an o-Nitrobenzyl Attached A1 Adenosine Receptor Antagonist, a Prodrug Approach.

ChemInform ◽  
2003 ◽  
Vol 34 (47) ◽  
Author(s):  
HeXi Chang ◽  
Carol Ensinger ◽  
Robert D. McCargar ◽  
Bruno M. Vittimberga
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist

scholarly journals Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 603
Author(s):  
Hyunseong Kim ◽  
Jin Young Hong ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
In-Hyuk Ha
Keyword(s):  
Phospholipase A2 ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neurological Diseases ◽  
Minor Component ◽  
Underlying Mechanism ◽  
Bee Venom ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Wide Range

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

scholarly journals Ganglioside GM1 Targets Astrocytes to Stimulate Cerebral Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Charles Finsterwald ◽  
Sara Dias ◽  
Pierre J. Magistretti ◽  
Sylvain Lengacher
Keyword(s):  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Brain Diseases ◽  
Mitochondrial Activity ◽  
Ganglioside Gm1 ◽  
Neuroprotective Effects ◽  
Wide Range ◽  
Cord Injury ◽  
Clinical Benefits ◽  
The Brain

Gangliosides are major constituents of the plasma membrane and are known to promote a number of physiological actions in the brain, including synaptic plasticity and neuroprotection. In particular, the ganglioside GM1 was found to have a wide range of preclinical and clinical benefits in brain diseases such as spinal cord injury, Huntington’s disease and Parkinson’s disease. However, little is known about the underlying cellular and molecular mechanisms of GM1 in the brain. In the present study, we show that GM1 exerts its actions through the promotion of glycolysis in astrocytes, which leads to glucose uptake and lactate release by these cells. In astrocytes, GM1 stimulates the expression of several genes involved in the regulation of glucose metabolism. GM1 also enhances neuronal mitochondrial activity and triggers the expression of neuroprotection genes when neurons are cultured in the presence of astrocytes. Finally, GM1 leads to a neuroprotective effect in astrocyte-neuron co-culture. Together, these data identify a previously unrecognized mechanism mediated by astrocytes by which GM1 exerts its metabolic and neuroprotective effects.

The adenosine receptor blocker aminophylline increases anoxic ethanol excretion in crucian carp

1991 ◽  
Vol 261 (4) ◽  
pp. R1057-R1060 ◽  
Author(s):  
G. E. Nilsson
Keyword(s):  
Oxygen Consumption ◽  
Energy Consumption ◽  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Crucian Carp ◽  
Receptor Blocker ◽  
Carassius Carassius ◽  
Adenosine Receptor Antagonist ◽  
Crucian Carp Carassius Carassius

By depressing energy consumption, anoxia-tolerant animals are thought to compensate for a reduced ability to produce energy during anoxia. Adenosine is an inhibitory neuromodulator in vertebrates and, hence, has the potential ability to depress energy consumption. Ethanol is the main metabolic end product in anoxic Carassius, and the present study shows that the rate of ethanol excretion in anoxic crucian carp (Carassius carassius L.) can be increased threefold by treatment with the adenosine receptor antagonist aminophylline (75 mg/kg). By contrast, the same dose of aminophylline did not increase the rate of routine oxygen consumption during normoxia. It is hypothesized that adenosine acts as a metabolic depressant during anoxia in crucian carp.

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