Modulation of cellular function by polyamines

Igarashi, Kazuei; Kashiwagi, Keiko

doi:10.1016/j.biocel.2009.07.009

Cited by 699 publications

(548 citation statements)

References 144 publications

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“…The function of spermine and spermidine in SRS disease etiology is not yet fully elucidated, but it might be speculated that the altered spermine/spermidine ratio may severely affect the balance between excitatory and inhibitory mechanisms and result in cerebral dysfunction such as epilepsy. Spermine and spermidine regulate brain glutamate receptors including N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors that are involved in excitatory synaptic transmission (Pegg 2009;Igarashi and Kashiwagi 2010). Spermine activates the endogenous phosphorylation and function of the GABA A receptor (SidAhmed-Mezi et al 2010).…”

Section: N 8 -Acetylspermidine As a Novel Potential Biomarker For Snymentioning

confidence: 99%

“…Furthermore both spermine and spermidine are potent blockers of voltage-gated Na + channels and their pharmacological depletion leads to increased epileptogenic activity in pyramidal neurons (Fleidervish et al 2008). Modulation of NMDA receptors was further implicated in the etiology of intellectual disability (Igarashi and Kashiwagi 2010;Pegg 2014). Other SRS phenotypic aspects such as osteoporosis and deafness are explained by the involvement of spermine and spermidine in the regulation of osteoclastic activity and endocochlear potential homeostasis (Wang et al 2009;Yamamoto et al 2012).…”

Section: N 8 -Acetylspermidine As a Novel Potential Biomarker For Snymentioning

confidence: 99%

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N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

Abela

Simmons

Steindl

et al. 2015

J of Inher Metab Disea

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Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic-metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N(8)-acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level. Abstract Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic-metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N 8 -acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level.

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Section: N 8 -Acetylspermidine As a Novel Potential Biomarker For Snymentioning

confidence: 99%

Section: N 8 -Acetylspermidine As a Novel Potential Biomarker For Snymentioning

confidence: 99%

N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

Abela

Simmons

Steindl

et al. 2015

J of Inher Metab Disea

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“…BAs are metabolites produced by the decarboxylation of amino acids (AAs), with significant physiological functions in eukaryotic cells as they are precursors for the synthesis of hormones, alkaloids, nucleic acids and proteins [6]. BAs such as histamine are immune mediators and neurotransmitters, whereas others, such as putrescine, spermidine and spermine, are needed for optimal cell growth and differentiation, stabilization of the DNA negative charge, RNA transcription, protein synthesis, apoptosis and regulation of the immune response [7–12]. In bacteria, BAs are also essential for growth and proliferation [13], but the concentrations produced and secreted are far higher than those of eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

A wide diversity of bacteria from the human gut produces and degrades biogenic amines

Pugin

Barcik

Westermann

et al. 2017

Microbial Ecology in Health and Disease

126

118

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Background: Biogenic amines (BAs) are metabolites produced by the decarboxylation of amino acids with significant physiological functions in eukaryotic and prokaryotic cells. BAs can be produced by bacteria in fermented foods, but little is known concerning the potential for microbes within the human gut microbiota to produce or degrade BAs.Objective: To isolate and identify BA-producing and BA-degrading microbes from the human gastrointestinal tract.Design: Fecal samples from human volunteers were screened on multiple growth media, under multiple growth conditions. Bacterial species were identified using 16S rRNA sequencing and BA production or degradation was assessed using ultra-performance liquid chromatography.Results: In total, 74 BA-producing or BA-degrading strains were isolated from the human gut. These isolates belong to the genera Bifidobacterium, Clostridium, Enterococcus, Lactobacillus, Pediococcus, Streptococcus, Enterobacter, Escherichia, Klebsiella, Morganella and Proteus. While differences in production or degradation of specific BAs were observed at the strain level, our results suggest that these metabolic activities are widely spread across different taxa present within the human gut microbiota.Conclusions: The isolation and identification of microbes from the human gut with BA-producing and BA-degrading metabolic activity is an important first step in developing a better understanding of how these metabolites influence health and disease.

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“…It interacts with nucleic acids in diverse and important ways, functioning as a protective agent (4)(5)(6)(7)(8) and a modulator of DNA secondary structure (9). In cells, spermine is largely bound to RNA, with between one and four bound spermine molecules per 100 RNA phosphates (2,10) (between 65% and 85% of the total spermine (9)). Crystal structures of spermine complexed with tRNA show spermine lying deep within the major groove (11).…”

Section: Introductionmentioning

confidence: 99%

Spermine Condenses DNA, but Not RNA Duplexes

Katz

Tolokh

Pabit

et al. 2017

Biophysical Journal

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Interactions between the polyamine spermine and nucleic acids drive important cellular processes. Spermine condenses DNA and some RNAs, such as poly(rA):poly(rU). A large fraction of the spermine present in cells is bound to RNA but apparently does not condense it. Here, we study the effect of spermine binding to short duplex RNA and DNA, and compare our findings with predictions of molecular-dynamics simulations. When small numbers of spermine are introduced, RNA with a designed sequence containing a mixture of 14 GC pairs and 11 AU pairs resists condensation relative to DNA of an equivalent sequence or to 25 bp poly(rA):poly(rU) RNA. A comparison of wide-angle x-ray scattering profiles with simulation results suggests that spermine is sequestered deep within the major groove of mixed-sequence RNA. This prevents condensation by limiting opportunities to bridge to other molecules and stabilizes the RNA by locking it into a particular conformation. In contrast, for DNA, simulations suggest that spermine binds externally to the duplex, offering opportunities for intermolecular interaction. The goal of this study is to explain how RNA can remain soluble and available for interaction with other molecules in the cell despite the presence of spermine at concentrations high enough to precipitate DNA.

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Modulation of cellular function by polyamines

Cited by 699 publications

References 144 publications

N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

A wide diversity of bacteria from the human gut produces and degrades biogenic amines

Spermine Condenses DNA, but Not RNA Duplexes

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Modulation of cellular function by polyamines

Cited by 699 publications

References 144 publications

N8‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

N8‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

A wide diversity of bacteria from the human gut produces and degrades biogenic amines

Spermine Condenses DNA, but Not RNA Duplexes

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Product

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N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

N⁸‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics