These studies are directed toward (1) determination of a) molecular distribution, localization of the gnomic peptides that cross-link and b) temporal sequence of formation and fate of the reducible intermediate imminium and ketoimine cross-links as collagen organizes into fibers and bundles and undergoes age-related changes, using the Ivalon sponge implant simply as a convenient easily manipulatable model system. (2) Measurement of stable non-reducible cross-link(s) densities in collagen, (3) molecular location of these stable collagen crosslinks and (4) investigating the hypothesis that the NaBH4 reducible imminium and keto-imine cross-links, which disappear with increasing age of collagenous tissues, are converted to stable non-reducible amine cross-links. Stabilization in the organization and packing of collagen into fibrillar matrices occurs with the formation of acid or heat labile reducible imminium covalent inter-molecular crosslinks. These initial crosslinks are transitory and intermediate in nature and with time and age go on to form or are replaced by more stable compounds. With the synthesis of the stable crosslinks, polymeric collagen in the matrix becomes more refractory and acquires a high tensile strength. These molecular alterations are believed to be strongly related to collagen matrix structure and physiological function. Attention will be directed toward the quantification and fate of dehydro-di hydroxylysinonorleucin (deH-DHLNL) crosslinked peptides in the tissue collagen of the sponge-implant model as a function of tissue age and sex differences. Major emphasis will be placed on the molecular location and distribution of these peptides. Investigations also involve the quantification and location in collagen matrices of the crosslinks hydroxyaldol-histidine (HAH) and 3-OH pyridinium because of the potential effects of maturational collagen stabilization on vascular tissues and on structure-function relationships. Tissue of animals undergoing aging will be examined exploiting the new methodology developed in the laboratory by the use of 14C acrylonitrile.
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