Radioprotection of DNA by spermine: a molecular modelling approach

Sy, D.; Hugot, S.; Savoye, C.; Ruiz, S; Charlier, Michel; Spotheim-Maurizot, M.

doi:10.1080/095530099139719

Cited by 39 publications

(4 citation statements)

References 42 publications

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“…Polyamines have many biological activities that may counteract the pathogenesis of aging-associated pathologies. For instance, they exert anti-inflammatory [ 49 , 121 , 124 , 125 , 126 , 127 , 128 ] and antioxidant properties [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]; protect cells and genes from harmful stimuli such as radiation [ 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 ], ultraviolet rays [ 148 , 149 , 150 ], toxic chemicals [ 128 , 151 , 152 , 153 , 154 ], and other stresses [ 148 , 155 , 156 , 157 ]; and they promote autophagy [ 128 , 158 , 159 ]. Very interestingly, polyphenols and antioxidant vitamins, which are abundant in legumes such as soybeans and in the Mediterranean diet, also have the same bioactivity as polyamines.…”

Section: Biological Activities Of Polyaminesmentioning

confidence: 99%

“…References for A circled: [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 25 , 26 , 28 , 29 , 30 , 31 ], References for B circled: [ 49 , 121 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 ], References for “?”: [ 22 , 25 , 26 , 27 , 28 , 30 , 31 …”

Section: Biological Activities Of Polyaminesunclassified

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Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation

Soda

2022

Cells

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Polyamines, spermidine and spermine, are synthesized in every living cell and are therefore contained in foods, especially in those that are thought to contribute to health and longevity. They have many physiological activities similar to those of antioxidant and anti-inflammatory substances such as polyphenols. These include antioxidant and anti-inflammatory properties, cell and gene protection, and autophagy activation. We have first reported that increased polyamine intake (spermidine much more so than spermine) over a long period increased blood spermine levels and inhibited aging-associated pathologies and pro-inflammatory status in humans and mice and extended life span of mice. However, it is unlikely that the life-extending effect of polyamines is exerted by the same bioactivity as polyphenols because most studies using polyphenols and antioxidants have failed to demonstrate their life-extending effects. Recent investigations revealed that aging-associated pathologies and lifespan are closely associated with DNA methylation, a regulatory mechanism of gene expression. There is a close relationship between polyamine metabolism and DNA methylation. We have shown that the changes in polyamine metabolism affect the concentrations of substances and enzyme activities involved in DNA methylation. I consider that the increased capability of regulation of DNA methylation by spermine is a key of healthy long life of humans.

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Section: Biological Activities Of Polyaminesmentioning

confidence: 99%

Section: Biological Activities Of Polyaminesunclassified

Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation

Soda

2022

Cells

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“…Polyamine-induced DNA compaction/aggregation is known to be a means of radioprotection (8, 10, 20). Thus, how SAT1, a rate-limiting enzyme of polyamine catabolism, would protect GBM cells from radiation is non-intuitive.…”

Section: Resultsmentioning

confidence: 99%

“…SAT1 catalyzes the acetylation of polyamines spermidine and spermine to form acetyl derivatives and is considered a rate-limiting enzyme in polyamine catabolism, leading to degradation or excretion (7). Paradoxically, polyamines, ubiquitous cationic molecules, are known radioprotectors through their capacity to compact DNA (8–10), confounding speculation of how SAT1 could promote resistance to radiation.…”

Section: Introductionmentioning

confidence: 99%

The Polyamine Catabolic Enzyme SAT1 Modulates Tumorigenesis and Radiation Response in GBM

et al. 2014

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Glioblastoma multiforme (GBM) is the most common and severe form of brain cancer. The median survival time of patients is approximately 12 months due to poor responses to surgery and chemoradiation. In order to understand the mechanisms involved in radioresistance, we conducted a genetic screen using an shRNA library to identify genes whose inhibition would sensitize cells to radiation. The results were cross-referenced with the Oncomine and Rembrandt databases to focus on genes that are highly expressed in GBM tumors and associated with poor patient outcomes. Spermidine/spermine-N1-acetyltransferase 1 (SAT1), an enzyme involved in polyamine catabolism, was identified as a gene that promotes resistance to ionizing radiation (IR), is overexpressed in brain tumors, and correlates with poor outcomes. Knockdown of SAT1 using shRNA and siRNA approaches in multiple cell and neurosphere lines resulted in sensitization of GBM cells to radiation in colony formation assays and tumors, and decreased tumorigenesis in vivo. Radiosensitization occurred specifically in G2/M and S phases, suggesting a role for SAT1 in homologous recombination (HR) that was confirmed in a DR-GFP reporter system. Mechanistically, we found that SAT1 promotes acetylation of histone H3, suggesting a new role of SAT1 in chromatin remodeling and regulation of gene expression. In particular, SAT1 depletion led to a dramatic reduction in BRCA1 expression, explaining decreased HR capacity. Our findings suggest that the biological significance of elevated SAT1 expression in GBM lies in its contribution to cell radioresistance and that SAT1 may potentially be a therapeutic target to sensitize GBM to cancer therapies.

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Effects of aminooxy analogues of biogenic polyamines on aggregation and stability of calf thymus DNA

Ramı́rez¹,

Antony²,

Ruiz-Chica³

et al. 2002

Biopolymers

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The effect of a series of aminooxy analogues of the biogenic polyamines spermidine and spermine on the conformation of calf thymus DNA is studied. These new molecules are isosteric and charge insufficient analogues that are suitable to study the roles of both charge distribution and structural requirements in the molecular physiology of the biogenic polyamines. They are also evidenced as useful tools to inhibit polyamine biosynthesis and cell growth. Circular dichroism (CD) spectra of solutions containing DNA and the aminooxy analogues at different concentrations (100-1000 microM) and different pH values, (5-7.5) are recorded. We use both sonicated and highly polymerized calf thymus DNA. The CD spectra of sonicated DNA showed the formation of Psi-DNA, a highly ordered aggregated structure similar to liquid crystals, in the presence of the aminooxy analogues. Aggregation induced by an aminooxy derivative of spermine is followed by DNA collapse when increasing the polyamine concentration. The features of Psi-DNA are not detected for highly polymerized DNA. Temperature melting measurements support a high degree of structural order of the aggregates. The CD experiments indicate that dications are unable to induce major changes on the macromolecular structure of DNA. In addition, aggregation is only observed when the trimethylene moiety is present between two adjacent positive charges. The observed differences among the CD spectra of DNA solutions with different aminooxy derivatives of spermidine indicate different roles for different amino groups of this biogenic polyamine when interacting with DNA. Our results support the idea that aminooxy analogues can be used as good models in studying the physiological functions of biogenic polyamines.

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Radioprotection of DNA by spermine: a molecular modelling approach

Abstract: Molecular modelling of DNA-spermine complexes that takes into account the electrostatic properties of DNA, allows an explanation of the experimentally observed effects of spermine on DNA radiosensitivity.

Cited by 39 publications

References 42 publications

Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation

Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation

The Polyamine Catabolic Enzyme SAT1 Modulates Tumorigenesis and Radiation Response in GBM

Effects of aminooxy analogues of biogenic polyamines on aggregation and stability of calf thymus DNA

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