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ECPB 2014, 68(4): 49–56
Clinical physiology and biochemistry

Peptids, as basis for creation of pharmacological preparations of directed action

RAKSHA N., SAVCHUK A., KONOPELNIUK V., OSTAPCHENKO L.
Abstract

This review summarizes current ideas about the composition and properties of «peptide pools». In accordance with the concept of «peptide pools» created by V. Ivanov, the proteolytic degradation of tissue proteins carried out by a specific and regulated system of tissue-specific enzymes and protein substrates gives rise to a large group of peptides, which define as tissue-specific «peptide pool». «Peptide pools» are stable at normal conditions, conservative in the same tissues of different mammalian species and dependent on the general state of homeostasis of tissue or the whole organism. Endogenous peptides present in tissue are proteolytically derived from a limited group of functional proteins such as myelin basic protein, fibronectin, g-globulins, cellular enzymes or from undefined protein precursors. The major source of peptides for «peptide pools» is hemoglobin.

Hemoglobin besides the transporting oxygen serves as a rich source of biologically active molecules which are generated by enzymatic hydrolysis of the alpha-, beta-globin chains of hemoglobin. The intraerythrocyte proteolysis is followed by the next degradation step coupled with excretion a number of newly formed shorter peptides from red blood cells. It should be noted that long as well as short hemoglobin fragments have properties that are not characteristic for parent molecule. The spectrum of the biological activities of tissue-specific peptides are similar to those described for some groups of endogenous peptide bioregulators – inhibition or stimulation of proliferation of normal and tumor cells; promotion of differentiation; induction of cytolysis; supporting the cell viability in the absence of growth factors. Tissue-specific peptides exhibit a variety of behavioral and physiological activities, their effects being realized predominantly at the tissue and cellular level. The molecular mechanisms of action of the majority of peptides are unknown. Hemorphins (hemoglobin-derived peptides) are established to bind to the same opioid receptors as neurotransmitters or hormones and to exhibit similar effects. Besides realization of the biological activity at the level of interaction with surface receptors the part of peptides are able to penetrate into the cell and the cell nucleus and activate the expression of a number of genes, including the telomerase gene. Since the intensity of proteolyses processes depends on such relatively conservative parameter as metabolic state of the organism the tissue specific «peptide pools» predominantly controls long-term processes that are responsible for maintenance of tissue homeostasis. The expressed biological activity and sensitivity of «peptide pools» to the physiological state of organism provides prospects for their analysis in the field of clinical diagnostics and prognostic information for cancer and other diseases. For example, the pathogenesis of some diseases is associated with the development of endogenous intoxication which greatly complicates the course of the underlying disease. A characteristic feature of endogenous intoxication syndrome is the accumulation in tissues and body fluids toxic medium-weight peptides.

In accordance with literature the appearance of medium-weight peptides under the development of the chronic alcohol intoxication syndrome can be result of activation of catabolic reaction, disturbance of their transportation to the excretory organs or decrease of detoxification system potential.

Keywords: peptidomica, «peptide pools», endogenous medium-weight peptides

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