Elastin turnover

Elastase prefers elastin as substrate if it is anionic in character, which is the case when anionic detergents or fatty acids are bound to elastin. Cationic detergents do not stimulate elastolysis. From the standpoint of elastin turnover in vivo a property of the protein which may provide protection from proteolytic enzymes resembling elastase is its cationic character (57,58). In fact, a significant feature of the protein that may protect against normal elastolysis is the observation that over 70% of the glutamyl and aspartyl residues in the protein appear to be amidated (58). 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

Therefore it is of interest to determine whether carotenoids can modulate the turnover of the extracellular matrix by the RPE by affecting the expression of MMPs, elastin, and/or collagen. Cultured RPE cells are a suitable model for such investigations. 

Elastogenesis occurs primarily during late fetal and early neonatal periods. Elastin is synthesized and secreted from several cell types including smooth muscle cells, fibroblasts, endothelial cells, chondroblasts, and mesothelial cells (Uitto et al, 1991) with tissue-specific induction of elastin expression during development (Swee et al, 1995). After elastin has been deposited, its synthesis ceases and very little turnover of elastin is seen during adult life, unless the elastic fibers are subject to injury. In this case,... 

Although nonenzymatic glycosylation may affect practically every protein in vivo, it is likely that nonenzymatic browning will occur only in proteins that have a slow turnover or none at all, such as lens crystallins, collagen, elastin and proteoglycans. In some tissues, these proteins are, in effect, "stored" for a lifetime and undergo some characteristic changes, many of which have been observed in stored and processed foodstuffs (Table II). 

The ECM that surrounds cells also contains variable levels of HA. It is composed predominantly of structural proteins such as collagen and elastin, as well as proteoglycans, and a number of glycoproteins. The HA content is greatest in embryonic ECM, and in tissues undergoing rapid turnover and repair. The basal lamina or basement membrane that separates dermis and epidermis is also considered an ECM structure. The basal lamina contains HA, though the precise structural position is not known. Loss of basement membrane HA in the skin of diabetic patients correlates with skin stiffness.50... 

When the metabolic turnover of elastin in arterial tissue or in lung is examined, it is extremely difficult to demonstrate active turnover. Once an elastin fiber is formed it appears to be fixed. The turnover of rat aorta elastin is best measured in years (8). Data shown in Figure 5 also suggests negliable turnover. The animal used for this study, the Japanese quail, was chosen because it fully matures at 5-6 weeks of age. Similar to the rat its elastin appears to turn over in amounts best estimated in years. 

Similar conclusions were reached by Kao et al. (1961) who injected female Wistar rats, 5 weeks, 8 months, and 2 years old with uniformly labeled Ci -lysine. The animals were sacrificed at intervals up to 40 days after injection. Elastin and collagen were isolated from aortas, tendon, uterus, and skin and examined for radioactivity. The results showed that with the exception of the uterus, insoluble collagen and elastin were synthesized at a significantly higher rate by 5-weeks-old rats than at 8 months or 2 years, but at all ages the turnover rate relative to other proteins was low. In agreement with the results of Slack, the elastin of aorta did not decay in activity in any age group above 5 weeks old. 

The work on metabolic turnover underlines the biological and chemical unreactivity of elastin which is perhaps its most characteristic property. Apart from the destructive effects of recognizable disease it has seemed to many authors that the mature elastic fiber, once laid down, is retained for life. In this situation it may be expected that changes may occur in elastic fibers which could be ascribed to the results of aging alone. Such changes have been looked for in a number of laboratories. 

Elastin is efficiently synthesized only in the fetus and children because it is normally extremely stable (half life 70 years). By contrast fibrillar collagens including those in bone have a turnover half-life of about 6 months. The failure to replace elastin causes the skin to become less elastic, more wrinkled, and thinner with age. 

The turnover rate of mature elastin in healthy persons is relatively low. Insoluble elastin in healthy elastic tissue is usually stable and subjected to minimal proteolytic degradation. In several clinical conditions (e.g., emphysema, advanced atherosclerosis, pancreatitis), increased degradation of fragmentation of elastic fibers may play a significant role. The interaction between insoluble elastin and soluble elastolytic enzymes, and the regulation of these enzymes, may shed light on certain cardiovascular diseases, in view of the role of elastin in arterial dynamics. 

I Reduced skin cell turnover Skin thinning due to the degradation of collagen and elastin... 

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