Biomol Ther.  2013 Jan;21(1):1-9.

Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases

• Park MH
• Igarashi K

Abstract

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

Keyword

Polyamine metabolites; Acrolein; Diacetylspemine; Diagnostic marker; Cancer; Stroke

MeSH Terms

Acrolein
Animals
Biomarkers
Brain Infarction
C-Reactive Protein
Diacetyl
DNA
Early Detection of Cancer
Eukaryotic Cells
Humans*
Hydrogen Peroxide
Inflammation
Interleukin-6
Lysine
Metabolism
Mice
Oxidative Stress
Oxidoreductases
Phospholipids
Plasma
Polyamines*
Putrescine
Renal Insufficiency
RNA
Sensitivity and Specificity
Spermidine
Spermine
Stroke
Acrolein
Biological Markers
C-Reactive Protein
DNA
Diacetyl
Hydrogen Peroxide
Interleukin-6
Lysine
Oxidoreductases
Phospholipids
Polyamines
Putrescine
RNA
Spermidine
Spermine