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Pure Appl. Chem., 2000, Vol. 72, No. 3, pp. 355-363

Tissue-specific peptide pools. Generation and function

Vadim T. Ivanov*, Oleg N. Yatskin, Olga A. Kalinina, Marina M. Philippova, Andrei A. Karelin and Elena Yu. Blishchenko Shemyakin-Ovchinnikov

Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117871 Moscow, Russia

Abstract: Systematic analysis of several tissue extracts for peptide components followed by bioactivity studies leads to formulation of the concept of "tissue-specific peptide pools". According to that concept the endogenous proteolysis of proteins with well-established functions, such as hemoglobin, actin, and cellular enzymes in tissues leads to formation of the sets (or pools) of bioactive peptides. The sets are tissue-specific on one hand and conservative in a given tissue at normal conditions on the other. The content and the composition of pool components are sensitive both to pathologies linked with alterations of tissue metabolism and to prolonged physiological changes. In vivo formation of fragments of functional proteins includes several consecutive proteolytic stages inside the cells and further release of bioactive compounds into the surrounding medium. The effects of pool components take place predominantly at tissue and cellular levels, their effects being related to stimulation or inhibition of cell growth, induction of cell differentiation, and death. The above-mentioned features lead to the proposal that the main in vivo function of components of tissue-specific peptides is maintenance of tissue homeostasis, i.e., the normal ratio of functional, dividing, differentiating, and dying cells of tissues. Components of tissue-specific peptide pools display several features distinguishing them from "classical" peptide hormones and neuromediators. Summarizing, a novel peptidergic regulatory system is considered.