Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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The Influence of Hypothalamic Cytokine PRP on Protein Synthesis in Brain Subcellular Compartments in Crush Syndrome

Author(s): Artashes G. Guevorkian, Alexander S. Kanayan, Gor G. Chailian, Kristine E.Danielyan, Hripsime L. Hayrapetyan, Karine A. Barsegyan, Hranush F. Khachatryan, Armen A. Galoyan, Guevork A. Kevorkian.

Abstract:

Crush-syndrom (CS) was characterized by Bywaters E.G.L. in 1941 after London blitz. The soft tissues is followed by acute hemodynamic shock, myoglobinuria, acute renal insufficiency, and lethal endotoxicity. Data of CS pathogenesis study has shown that the largest changes in Crush occur during decompression and are accompanied by acute alteration of brain protein synthesis and strong morphological changes of brain structures. The period of decompression might be characterized by the proteolytic breakdown of the myoglobine and formation of toxic peptides. In our current work we have identified four newly formed peptides in the brain of the animals subjected to the experimental muscle tissue injury. Our investigations related with the CS experimental model have demonstrated that during the 2-hours compression protein synthesis was decreased in cytosol (32,7%) and mitochondria (49%), after 5-h compression there were registered non-significant changes in the level of protein synthesis. Intraperitoneal administration of Proline-rich peptide, ((PRP), 1 mcg/100g weight of rats), originating from proteolysis of C-terminal glycoprotein a neurophysin II along with vasopressin and oxytocin and transferring from the hypothalamus to the neurohypophysis by axonal transport, initiates activation of the protein synthesis in all studied cellular subcomponents of brain cells. The positive effect of the peptide is conditioned, most probably, by activation of the immune system and adaptation mechanisms, including mobilization of endogen-protective mechanisms of the organism.

Keywords: Crush syndrome, brain, protein synthesis, brain mitochondria, brain endoplasmic reticulum, brain cytosol, prolinerich peptide, myoglobin

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Article Details

VOLUME: 11
ISSUE: 3
Year: 2011
Page: [184 - 188]
Pages: 5
DOI: 10.2174/187152411798047753
Price: $58