Search results for "guanosine"
showing 10 items of 171 documents
Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA
1996
Mitochondria may be primary targets of free radical damage associated with aging. We have found that mitochondrial glutathione is markedly oxidized with aging in rats and mice. The oxidized to reduced glutathione ratio rises with aging in the liver, kidney, and brain. The magnitude of these changes is much higher than that previously found in whole cells of any species previously studied. In the liver, this ratio (expressing GSSG as a percent of GSH) changed from 0.77 +/- 0.19% (n=5) in young rats to 2.47 +/- 1.25% (n=5) in old ones, i.e., 320% of the controls. In the brain and kidney, values for old rats were, respectively, 600 and 540% higher than those of young rats. A marked oxidation o…
Guanosine negatively modulates the gastric motor function in mouse
2013
The aim of the present study was to evaluate if guanine-based purines may affect the gastric motor function in mouse. Thus, the influence of guanosine on the gastric emptying rate in vivo was determined and its effects on spontaneous gastric mechanical activity, detected as changes of the intraluminal pressure, were analyzed in vitro before and after different treatments. Gastric gavage of guanosine (1.75-10 mg/kg) delayed the gastric emptying. Guanosine (30 μM-1 mM) induced a concentration-dependent relaxation of isolated stomach, which was not affected by the inhibition of the purine nucleoside phosphorylase enzyme by 4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-H. The inhibitory …
Reactive oxygen species derived from the mitochondrial respiratory chain are not responsible for the basal levels of oxidative base modifications obs…
2004
The mitochondrial electron transport chain (ETC) is the most important source of reactive oxygen species (ROS) in mammalian cells. To assess its relevance to the endogenous generation of oxidative DNA damage in the nucleus, we have compared the background (steady-state) levels of oxidative DNA base modifications sensitive to the repair glycosylase Fpg (mostly 7,8-dihydro-8-oxoguanine) in wild-type HeLa cells and HeLa rho0 cells. The latter are depleted of mitochondrial DNA and therefore are unable to produce ROS in the ETC. Although the levels of ROS measured by flow cytometry and redox-sensitive probes in rho0 cells were only 10-15% those of wild-type cells, steady-state levels of oxidativ…
A modified dinucleotide motif specifies tRNA recognition by TLR7
2014
RNA can function as a pathogen-associated molecular pattern (PAMP) whose recognition by the innate immune system alerts the body to an impending microbial infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends on its modification patterns. In particular, it is known that the presence of a ribose methylated guanosine at position 18, which is overrepresented in self-RNA, antagonizes an immune response. Here, we report that recognition extends to the next downstream nucleotide and the effectively recognized molecular detail is actually a methylated dinucleotide. The most efficient nucleobases combination of this motif includes two purines, while pyrimidines diminish t…
Structural insights into the GTPase domain of Escherichia coli MnmE protein
2007
The Escherichia coli MnmE protein is a 50-kDa multidomain GTPase involved in tRNA modification. Its homologues in eukaryotes are crucial for mitochondrial respiration and, thus, it is thought that the human protein might be involved in mitochondrial diseases. Unlike Ras, MnmE shows a high intrinsic GTPase activity and requires effective GTP hydrolysis, and not simply GTP binding, to be functionally active. The isolated MnmE G-domain (165 residues) conserves the GTPase activity of the entire protein, suggesting that it contains the catalytic residues for GTP hydrolysis. To explore the GTP hydrolysis mechanism of MnmE, we analyzed the effect of low pH on binding and hydrolysis of GTP, as well…
Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms
2021
Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors r…
In human and rat lung membranes [35s]GTPγS binding is a tool for pharmacological characterization of G protein-coupled devucleotide receptors
1999
The P2Y receptor family is activated by extracellular nucleotides such as ATP and UTP. P2Y receptors regulate physiological functions in numerous cell types. In lung, the P2Y2 receptor subtype plays a role in controlling Cl- and fluid transport. Besides ATP or UTP, also diadenosine tetraphosphate (Ap4A), a stable nucleotide, seems to be of physiological importance. In membrane preparations from human and rat lung we applied several diadenosine polyphosphates to investigate whether they act as agonists for G protein-coupled receptors. We assessed this by determining the stimulation of [35S]GTPgammaS binding. Stimulation of [35S]GTPgammaS binding to G proteins has already been successfully ap…
Postsynaptic NO/cGMP Increases NMDA Receptor Currents via Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in the Hippocampus
2013
The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling cascade participates in the modulation of synaptic transmission. The effects of NO are mediated by the NO-sensitive cGMP-forming guanylyl cyclases (NO-GCs), which exist in 2 isoforms with indistinguishable regulatory properties. The lack of long-term potentiation (LTP) in knock-out (KO) mice deficient in either one of the NO-GC isoforms indicates the contribution of both NO-GCs to LTP. Recently, we showed that the NO-GC1 isoform is located presynaptically in glutamatergic neurons and increases the glutamate release via hyperpolarization-activated cyclic nucleotide (HCN)-gated channels in the hippocampus. Electrophysiologi…
Inflammation in the Human Periodontium Induces Downregulation of the α1- and β1-Subunits of the sGC in Cementoclasts
2021
Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the &alpha
Inhibition of uterine contractility by guanine-based purines in non-pregnant rats
2022
Growing evidence pointed out that guanine-based purines are able to modulate smooth muscle contractile activity of blood vessels and gastrointestinal tract. Since, so far, possible guanine-based purine modulation of uterine musculature is unknown, the aim of the present study was to investigate in vitro, using organ bath technique, guanosine and guanine efects on spontaneous uterine contraction, and uterine contraction induced by K+-depolarization and oxytocin in a non-pregnant rat. Guanosine, but not guanine, reduced the amplitude of spontaneous contraction of the uterine muscle in a dose-dependent manner. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine (NBTI), a…