DNA and nuclear aggregates of polyamines

Iacomino, Giuseppe; Picariello, Gianluca; D’Agostino, Luciano

doi:10.1016/j.bbamcr.2012.05.033

Cited by 78 publications

(63 citation statements)

References 91 publications

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“…Thus, polyamines may act as ligands at multiple sites on DNA, RNA, proteins, phospholipids and nucleotide triphosphates (4). Accordingly, biological functions of polyamines are mainly involved in the regulation of gene expression by altering DNA structure and modulating signal transduction pathways (5,6).…”

Section: Polyamine Metabolism and Colorectal Cancermentioning

confidence: 99%

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

Linsalata¹,

Orlando²,

Russo³

2014

International Journal of Oncology

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Abstract. Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of colorectal tumorigenesis. Consequently, polyamine biosynthesis and catabolism can be considered as promising targets for cancer chemoprevention. A variety of drug formulations have been tested for their efficacy in affecting polyamines in a strategy of colorectal cancer prevention. Different molecules, such as biosynthesis inhibitors and catabolism inducers, have been proposed alone or in combination with other drugs proved to diminish the colorectal cancer risk. Interestingly, also diet can play a role in cancer prevention by affecting polyamines. Several dietary components, such as probiotics or flavonoids, have been shown to affect the polyamine metabolic pathway in colorectal neoplastic tissue. On the other hand, the polyamines ingested with diet might contrast the above cited effects shown by both drugs and nutritional factors. It is, therefore, fundamental to acquire more data also on these aspects in view of an innovative approach to colorectal oncology. This review summarizes data on the role of polyamine metabolism in neoplastic transformation of colorectal mucosa and as possible target for colorectal cancer chemoprevention. Attention will be focused on the influence of drugs and nutritional factors on polyamine metabolism, as well as the role played by dietary polyamines.

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Section: Polyamine Metabolism and Colorectal Cancermentioning

confidence: 99%

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

Linsalata¹,

Orlando²,

Russo³

2014

International Journal of Oncology

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“…Natural polyamines are aliphatic nitrogenous bases which at physiological pH are predominately positively charged. They are present in all cells and associate with nucleic acids to help direct a variety of RNA [23] and DNAmediated processes [24,25]. Conjugation of polyamines to oligonucleotides creates zwitterionic functionality, which can enhance both nucleic acid target hybridization and cellular penetration, in a similar fashion as the polyamine polyethyleneimine (PEI), which is a useful transfection reagent [26][27][28].…”

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confidence: 99%

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

2015

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Chemical modification and/or the conjugation of small functional molecules to oligonucleotides have significantly improved their biological and biophysical properties, addressing issues such as poor cell penetration, stability to nucleases and low affinity for their targets. Here, the authors review the literature reporting on the biophysical, biochemical and biological properties of one particular class of modification - polyamine-oligonucleotide conjugates. Naturally derived and synthetic polyamines have been grafted onto a variety of oligonucleotide formats, including antisense oligonucleotides and siRNAs. In many cases this has had beneficial effects on their properties such as target hybridization, nuclease resistance, cellular uptake and activity. Polyamine-oligonucleotide conjugation, therefore, represents a promising direction for the further development of oligonucleotide-based therapeutics and tools.

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“…1, top center), medium NAPs (m-NAP, Fig. 1, bottom center), and large NAPs (l-NAP, not shown) of approximately 1, 5, and 8 kDa, respectively [76][77][78][79]. The exact structures are not known but are believed to be ring-like for s-NAPs with one putrescine, one spermidine, and two spermines along with phosphate ions.…”

Section: Napsmentioning

confidence: 92%

A Review of Autoimmune Disease Hypotheses with Introduction of the “Nucleolus” Hypothesis

Brooks

2016

Clinic Rev Allerg Immunol

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Numerous hypotheses have been proposed in order to explain the complexity of autoimmune diseases. These hypotheses provide frameworks towards understanding the relations between triggers, autoantigen development, symptoms, and demographics. However, testing and refining these hypotheses are difficult tasks since autoimmune diseases have a potentially overwhelming number of variables due to the influence on autoimmune diseases from environmental factors, genetics, and epigenetics. Typically, the hypotheses are narrow in scope, for example, explaining the diseases in terms of genetics without defining detailed roles for environmental factors or epigenetics. Here, we present a brief review of the major hypotheses of autoimmune diseases including a new one related to the consequences of abnormal nucleolar interactions with chromatin, the "nucleolus" hypothesis which was originally termed the "inactive X chromosome and nucleolus nexus" hypothesis. Indeed, the dynamic nucleolus can expand as part of a cellular stress response and potentially engulf portions of chromatin, leading to disruption of the chromatin. The inactive X chromosome (a.k.a. the Barr body) is particularly vulnerable due to its close proximity to the nucleolus. In addition, the polyamines, present at high levels in the nucleolus, are also suspected of contributing to the development of autoantigens.

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DNA and nuclear aggregates of polyamines

Cited by 78 publications

References 91 publications

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

A Review of Autoimmune Disease Hypotheses with Introduction of the “Nucleolus” Hypothesis

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