On the role of cross-linking of cellular proteins in aging.
Water-insoluble protein fractions increase in the brain cortical tissue and liver of rats during aging in both sexes. This suggests a possible increase in the cross-linking of proteins which may be due to the formation of, for example, hydroxyl free radicals during several metabolic processes. In vivo application of centrophenoxine causes a reversal of this phenomenon in old rats. In vitro experiments show that the generation of hydroxyl free radicals by chemical systems like homolysis of H2O2 by redox coupling with Fe2+ leads to Fe3+ conversion, results in the cross-linking of bovine serum albumin and the mixed proteins of liver or brain homogenates of young rats. The cross-linked proteins have a very much increased molecular weight, they become mostly insoluble even in 6 M urea. Dimethylaminoethanol, the effective part of the centrophenoxine molecules, is able to diminish the extent of cross-linking, acting most probably as a free-radical scavenger. The results are discussed in terms of the "membrane hypothesis of aging". A molecular basis is proposed for the anti-aging effect of centrophenoxine.
D000375:Aging / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003642:Deanol / Q000494:pharmacology; D005296:Ferrous Compounds / Q000378:metabolism; D005609:Free Radicals; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012995:Solubility
D005296:Ferrous Compounds; D005609:Free Radicals; D046911:Macromolecular Substances; D011506:Proteins; D012710:Serum Albumin, Bovine; D003642:Deanol