Possible mechanism of 6-methyl-2-ethyl-3-oxypyridine age-dependent effect on protein synthesis in the brain.

Abstract

Intraperitoneal injection of different amounts of 6-methyl-2-ethyl-3-oxypyridine (6M2E3OP) to 3- and 18-month old rats led to significant reduction of translating activity in vitro of membrane-bound polysomes of rat brain cells, but not of free polysomes. This regularity is more marked in the case of endoplasmic membranes of 18-month old than those of 3-month old animals. Separation of polysomes from membranes by Triton X-100 resulted in restoration of template activity of the former to the level of free polysomes. 48 h after intraperitoneal injection of 6M2E3OP to 3- and 18-month old rats, the substance is found by special HPLC technique only in endoplasmatic reticulum membranes of brain cells, but not in cytoplasm. The xenobiotic does not change the age-dependent quantitative ratio of free and membrane-bound polysomes of the brain. At the same time the substance significantly inhibits the mean rate of synthesis of the longest polypeptide chains (Mol. weight 28-42,000) in cells of old animals, unlike this rate in adult rats. Analysis of the obtained data and literature data permit us to make a conclusion on the ability of this xenobioticselectively to modulate a membrane-associated protein synthesis in the brain.