Levels of Protein Carbonylation and Activity of Proteases in the Brain of Newborn Rats with Prenatal Hyperhomocysteinemia

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Abstract
—Homocysteine is a sulfur-containing amino acid formed from methionine and considered as a risk factor for a number of pathologies. An increase in the homocysteine level (hyperhomocysteinemia, HHcy) during pregnancy leads to various complications of pregnancy, fetal hypoxia and, consequently, development of early and delayed postnatal pathologies. One of the main mechanisms of homocysteine action is induction of oxidative stress. The aim of our study was to analyze oxidative modification of proteins and activity of proteases, as well as the level of oxidative stress in the brain tissue of rats with prenatal HHcy in the first week after birth. Experimental HHcy was induced in female rats by feeding them with elevated amounts of methionine for 3 weeks before, during, and after pregnancy. In the homogenates of brain tissue of offspring with prenatal HHcy a significant increase in spontaneous protein carbonylation was observed. This result indicates a decrease in the reserve-adaptive potential of brain cells and a decrease in the resistance of the tissue to the action of free radicals. In the brains of rats with prenatal HHcy, the activity of acidic and neutral proteases was higher compared to controls which could be a result of aggregation and fragmentation of protein molecules due to carbonylation of amino acid residues. Brain tissues of newborn rats with prenatal HHcy were also characterized by a high content of hydrogen peroxide, malondialdehyde as the marker of lipid peroxidation, and a decrease in the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Thus, the data obtained indicate a significant increase in the irreversible process of oxidative modification of proteins in the brain of newborn rats with prenatal HHcy due to oxidative stress. These processes contribute to the mechanisms of homocysteine neurotoxicity during the critical period of brain development in the early postnatal period, during which intensive neurogenesis, synaptogenesis, and formation of neural networks take place.

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