Search results for "spermidine"
showing 10 items of 38 documents
The acetylation of spermidine catalyzed by P/CAF regulates its acetyltransferase activity versus histones
2010
Transcriptional regulation in eukaryotes occurs within a chromatin setting and is strongly inhibited by nucleosomal barriers imposed by histone proteins. Among the well-known covalent modifications of chromatin, the reversible acetylation of specific lysine residues of histones, catalyzed by several acetyltransferase and deacetylases, has been linked to many biological processes including transcriptional regulation. Indeed, many transcriptional coactivators possess histone acetyltransferase (HAT) activity (1). Functional interactions between HAT and polyamines have been previously reported. In particular, it has been shown that polyamines facilitate oligomerization of nucleosomal arrays in …
Regulatory effects of polyamines on membrane-bound acetylcholinesterase
1974
The effects of putrescene, spermidine and spermine on membrane-bound acetylcholinesterase from human erythrocyte ‘ghosts’ and the solubilized enzyme of the electric organ of the electric eel were studied by kinetic methods. Measurements were made by using a photometric method which made it possible to record the enzyme reaction in the steady-state phase. Substrate-concentration-dependent activation and inhibition of acetylcholinesterase by polyamines is similar to that by Na+, K+, Ca2+, Mg2+ and certain quaternary and bisquaternary amines. The kinetics suggest an allosteric reaction mechanism. On the basis of the kinetic results a role for the polyamines as modulators of synaptic acetylchol…
New insights into the role of spermine in Arabidopsis thaliana under long-term salt stress
2010
Polyamines (putrescine, spermidine and spermine) are traditionally implicated in the response of plants to environmental cues. Free spermine accumulation has been suggested as a particular feature of long-term salt stress, and in the model plant Arabidopsis thaliana the spermine synthase gene (AtSPMS) has been reported as inducible by abscisic acid (ABA) and acute salt stress treatments. With the aim to unravel the physiological role of free spermine during salinity, we analyzed polyamine metabolism in A. thaliana salt-hypersensitive sos mutants (salt overlay sensitive; sos1-1, sos2-1 and sos3-1), and studied the salt stress tolerance of the mutants in spermine and thermospermine synthesis …
PCAF catalyzes tha acetylation of spermidine to N8-acetylspermidine and regulates its acetylating activity on histones
2011
Post-transcriptional histone acetylation is a well known process playing a crucial role in chromatin assembly and transcription. Here, we report that PCAF, a highly conserved histone acetyltransferase (HAT), can efficiently catalyze acetylation of spermidine to N8-acetylspermidine, at low concentration. Remarkably, we found that spermidine at higher concentration can also inhibit PCAF HAT activity directed against histone H3 in vitro, confirming the in vivo data referred by Eisenberg et al. on the spermidine induced inhibition of H3 acetylation. Surprisingly when we performed HAT assay experiments at low spermidine concentration we observed an activating effect on PCAF on H3 acetylation. Ou…
Production of Norspermidine Contributes to Aminoglycoside Resistance in pmrAB Mutants of Pseudomonas aeruginosa
2019
Emergence of resistance to polymyxins in Pseudomonas aeruginosa is mainly due to mutations in two-components systems, that promote addition of 4-amino-4-deoxy-L-arabinose to the lipopolysaccharide (LPS) through upregulation of operon arnBCADTEF-ugd (arn) expression. Here, we demonstrate that mutations occurring in different domains of histidine kinase PmrB or in response regulator PmrA result in coresistance to aminoglycosides and colistin. All seventeen clinical strains tested exhibiting such a cross-resistance phenotype were found to be pmrAB mutants. As shown by gene deletion experiments, the decreased susceptibility of the mutants to aminoglycosides was independent from operon arn but r…
Regulation of PCAF Activity by Spermidine
2011
Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy a…
Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by mitoxantrone.
2013
T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It is involved in the negative regulation of many cellular signaling pathways. Thus, activation of TCPTP could have important therapeutic applications in diseases such as cancer and inflammation. We have previously shown that the α-cytoplasmic tail of integrin α1β1 directly binds and activates TCPTP. In addition, we have identified in a large-scale high-throughput screen six small molecules that activate TCPTP. These small molecule activators include mitoxantrone and spermidine. In this study, we have investigated the molecular mechanism behind agonist-induced TCPTP activation.…
Influence of agents that act on DNA and RNA synthesis on the activity of poly(ADP-Rib) polymerase
1975
The activity of poly(ADP-Rib) polymerase is enhanced in the presence of spermine and spermidine. Among the adenosine-like antibiotics tested, only formycin B and showdomycin cause an inhibition of the enzyme, which is competitive to NAD. The activity of poly(ADP-Rib) polymerase is not reduced by rifamycin, alpha-amanitin and 2-phenylethanol.
Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes
2018
Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…
Pattern of polyamines and related monoacetyl derivatives in chick embryo retina during development.
1994
Polyamines and related monoacetyl derivatives were studied in chick embryo retina during development (6th-19th day). Putrescine, which is high in the first phase of retinogenesis, is necessary to sustain both tissue proliferation and via N-acetylputrescine, gamma-aminobutyric acid synthesis. A later increase in spermidine and particularly spermine may play a role in the last phase of development when the retina reaches maturation. The presence of N1-acetylspermidine already at the 8th day indicates that in chick embryo retina, putrescine synthesis can depend on two separate pathways. The first involves ornithine decarboxylase activity; the second, spermidine/spermine N1-acetyltransferase an…