The lipochrome pigment of molluscan neurons as a specific electron acceptor.
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Biomedical subjects
Publications and source records attributed to I Zs-Nagy.
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The turnover of proteins in biological systems is due mostly to an ever-occurring damaging (cross-linking) effect of the OH. free radicals. The replacement of the damaged proteins requires a continuous gene expression. A key issue of experimental gerontology is why the gene expression maintains the fidelity but loses the speed during aging. The membrane hypothesis of aging (MHA) proposes a cellular mechanism based on the fact that the more compact cellular structures (e.g., membranes) are damaged faster than the more diluted ones (e.g., cytosol). In addition, the cell membrane is exposed also to the residual heat-induced damage deriving from a frequent discharge of its electric polarity. Therefore, one can assume that even an extremely small incompleteness of the replacement of the damaged membrane components per turnover cycle may result in an error accumulation, which may be responsible first for the inhibition of growth, then for aging of cells. In agreement with this hypothesis, neurons display a life-long, gradual loss of the passive potassium permeability of the cell membrane, resulting in a continuous dehydration of the intracellular mass, i.e., an increase of physical density. Theory and experimental models show that this latter process causes a slowing down of all enzyme functions including those realizing the gene expression and the elimination of the damaged components. Increase of the dry mass content of cells and tissues is an obligatory process for maturation; however, later on it leads to aging. The known nootropic effects of centrophenoxine (CPH) can be interpreted on the basis of the OH. radical scavenger properties of dimethylaminoethanol (DMAE) which is incorporated in the neuronal membranes of the brain in form of phosphatidyl-DMAE. The protective effects of CPH (and of similar, newly synthesized other drugs) on the membrane components can slow down the age-dependent deteriorations of the intracellular physicochemistry, in agreement with the predictions of the MHA.
Female CFY rats (21 months old) and male spontaneously hypertensive, stroke-prone (SHRsp) rats (3 months old), in conventional housing conditions, received placebo (5% gum arabic solution) or 50 mg/kg bw/day idebenone suspended in 5% gum arabic, through a gastric tube for 5 weeks; then their brains were elaborated as follows: (1) Total proteins as well as water-soluble and water-insoluble proteins (WSP and WIP, respectively) were separated from the brain homogenate by centrifugation at 500 X g. The WIP fractions were tested also in vitro by heat denaturation at 64 degrees C (10 min) and by 3 M urea treatment. In the placebo group of CFY rats the total protein content was 113.9 mg per g fresh weight. WIP amounted to 27.2% of the total proteins. Idebenone-treatment did not alter the protein composition in these old rats. In the SHRsp rats the total protein content of the brain cortex was almost identical with that of the normal, Wistar-derived CFY rats of much more advanced age (about 2 years). The idebenone-treatment did not alter the protein content of the brain cortex, although the WIP content and the heat-resistant fraction of it increased significantly in this strain. (2) The osmotic potential of brain tissue was determined by measuring swelling or shrinkage velocities in Ringer solution, the osmotic concentration of which was rendered hypo- or hyperosmotic by dilution or addition of polythylene glycol (PEG 6000), respectively. Idebenone treatment exerted no effect on the osmometric properties of the brain tissue in either the normal old or the SHRsp rats.
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