Structural Biology 2018: THE ROLE OF POLYAMINES AS THE ONCOMARKERS IN THE BLOOD - Christina Sungrapova - Рeoples Friendship University of Russia | Abstract
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Structural Biology 2018: THE ROLE OF POLYAMINES AS THE ONCOMARKERS IN THE BLOOD - Christina Sungrapova - Рeoples Friendship University of Russia

Author(s): Christina Sungrapova

The content of polyamines in the blood is of interest now not only to researchers however also to practising physicians. The ranges of polyamines in the blood had been examined as nonspecific cancer markers. However, like most different putative biochemical markers, they did not go into medical practice because there was no simple, commercially available, low-cost, positive approach for deciding these compounds in the blood. Most of the techniques currently used for the evaluation of polyamines have extraordinary sensitivity and accuracy, require costly and complicated equipment. Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are quintessential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate a number cellular features such as macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological stipulations such as cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is regularly 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 increased in the urine of most cancers patients and current conceivable markers for early detection. Enhanced catabolism of cell polyamines by means of polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cell oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently contains into lysine residues of cell proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes had been increased in the locus of Genius infarction and in plasma in a mouse model of stroke and additionally in the plasma of stroke patients. When the blended measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) have been evaluated, even silent brain infarction (SBI) was once detected with high sensitivity and specificity. Considering that there are no dependable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine grant useful tools in early prognosis of cancer and stroke. The polyamines, putrescine [NH2(CH2)4NH2], spermidine [NH2(CH2)4NH(CH2)3NH2] and spermine [NH2(CH2)3NH(CH2)4 NH(CH2)3NH2], are organic polycations present in all eukaryotes and are quintessential for cell proliferation. Since their main and secondary amino corporations are protonated at physiological pH, these polyamines engage electrostatically with negatively charged molecules such as DNA, RNA, proteins and phospholipids and they have been proposed to modify cell activities at transcriptional, translational and post-translational levels. The polyamines fluctuate from inorganic cations like Mg2+ or Ca2+ in that their effective fees are spaced at defined distances by bendy methylene chains that can participate in hydrophobic interactions. Thus polyamines interact in improved and extra particular interactions with nucleic acids and acidic macromolecules than inorganic cations do. Although net cell concentrations of polyamines are commonly at millimolar tiers in eukaryotic cells, most intracellular polyamines are compartmentalized and/or sure to nucleic acids and different negatively charged molecules. Hence, the concentrations of free polyamines are much lower than the total cell concentration. Normally, polyamine homeostasis is elaborately maintained through intricate more than one remarks mechanisms at the stages of biosynthesis, catabolism, uptake and efflux. Over-accumulation of polyamines has been associated with cell transformation or apoptosis, whereas their reduction/depletion leads to inhibition of cell growth, migration, and embryonic development. Enhanced ranges of polyamines and polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) are frequently associated with hyper-proliferation and cancer. NIH3T3 cells over-expressing ODC are tumorigenic in nude mice and elevated expression of ODC enhances tumor improvement in initiated premalignant epidermal cells. Activation of the polyamine catabolic pathway reasons an improved oxidative stress and additionally may additionally contribute to aging and pathological conditions ensuing from cellular damages.