Toxicity of polyamines and their metabolic products

Research output: Contribution to journalReview article

81 Citations (Scopus)

Abstract

Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease.

Original languageEnglish (US)
Pages (from-to)1782-1800
Number of pages19
JournalChemical Research in Toxicology
Volume26
Issue number12
DOIs
StatePublished - Dec 16 2013

Fingerprint

Polyamines
Toxicity
Cellular Structures
Cells
Acrolein
Proteins
Spermine
Poisons
Liver Neoplasms
Metabolites
Macromolecules
Ion Channels
Gene expression
Aldehydes
Liver
Nucleic Acids
Hydrogen Peroxide
Renal Insufficiency
Liver Diseases
Early Diagnosis

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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Toxicity of polyamines and their metabolic products. / Pegg, Anthony.

In: Chemical Research in Toxicology, Vol. 26, No. 12, 16.12.2013, p. 1782-1800.

Research output: Contribution to journalReview article

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AU - Pegg, Anthony

PY - 2013/12/16

Y1 - 2013/12/16

N2 - Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease.

AB - Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease.

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