Glycosaminoglycans, proteoglycans and aging

Sames, K.

doi:10.1007/978-3-0348-7545-5_14

Cited by 4 publications

(3 citation statements)

References 146 publications

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“…Few conflicting data regarding the relationship between plasma GAG content and ageing are present in the literature. Some investigations found that total plasma GAG content does not vary with age [ 30 , 31 ]. Conversely, a positive correlation between total plasma GAG levels and age has been reported in males [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Zinellu

Lepedda

Cigliano

et al. 2012

Biochemistry Research International

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Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P < 0.01) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

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Section: Discussionmentioning

confidence: 99%

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Zinellu

Lepedda

Cigliano

et al. 2012

Biochemistry Research International

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“…It has been shown that the ratios of GAGS within tissues undergo significant changes during development and aging (45)(46)(47)(48)(49). For example, heparanase, which primarily hydrolyzes HS but also C-4S, is highly expressed in various tumor cells and strongly facilitates tumor invasion and tumor angiogenesis (50).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Collagenase Activities of Human Cathepsins by Glycosaminoglycans

Yasuda

et al. 2004

Journal of Biological Chemistry

212

210

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Cathepsin K, a lysosomal papain-like cysteine protease, forms collagenolytically highly active complexes with chondroitin sulfate and represents the most potent mammalian collagenase. Here we demonstrate that complex formation with glycosaminoglycans (GAGs) is unique for cathepsin K among human papain-like cysteine proteases and that different GAGs compete for the binding to cathepsin K. GAGs predominantly expressed in bone and cartilage, such as chondroitin and keratan sulfates, enhance the collagenolytic activity of cathepsin K, whereas dermatan, heparan sulfate, and heparin selectively inhibit this activity. Moreover, GAGs potently inhibit the collagenase activity of other cysteine proteases such as cathepsins L and S at 37°C. Along this line MMP1-generated collagen fragments in the presence of GAGs are stable against further degradation at 28°C by all cathepsins but cathepsin K, whereas thermal destabilization at 37°C renders the fragments accessible to all cathepsins. These results suggest a novel mechanism for the regulation of matrix protein degradation by GAGs. It further implies that cathepsin K represents the only lysosomal collagenolytic activity under physiologically relevant conditions.Controlled degradation of collagen is observed in bone remodeling, wound healing, angiogenesis, and during organ development (1-3). On the other hand excessive collagen degradation leads to pathological phenotypes such as osteoporosis (4), various forms of arthritis (5), or aneurysms of blood vessels (6), or it is characteristic for tumor invasion (7). However, triple helical collagens, in particular type I and II collagens, are highly resistant to general proteolysis and require specific proteases for their degradation. Known mammalian collagenolytic activities include members of the matrix metalloprotease family such as MMP-1, -2, -8, -13, and -14 (8), the serine protease, human neutrophil elastase (9), and thiol-dependent cathepsins (1). Collagenases of the MMP family cleave triple helical collagen at a specific single site and release 3 ⁄4 and 1 ⁄4 fragments. Similar to MMPs, human neutrophil elastase generates 3 ⁄4 fragments from type I collagen but is unable to degrade type II collagen (9). Lysosomal cysteine proteases such as cathepsins L and B have also been discussed as collagenolytic activities, but these data were mostly based on inhibitor experiments in cell extracts or on early preparations of cathepsins, which may not have excluded contaminating activities (10 -13). Thorough enzymatic studies suggested that cathepsins B and L primarily cleave in the non-helical telopeptide extensions of collagens (14, 15). A truly triple helical collagenase activity is found in cathepsin K, which is predominantly expressed in osteoclasts and to a lower degree in various other cell types including fibroblasts (16 -19). It was demonstrated that cathepsin K, similar to the bacterial Clostridium collagenase, cleaves at multiple sites within the triple helical region of types I and II collagens (20,21). The biological relevan...

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“…The fine structure of PGs have been reported to change as a function of donor age in other organ systems (13). The current study was undertaken to determine whether post-translational modifications to PGs can serve as surrogate biochemical markers to define donor chronological age.…”

Section: Osteogenesis Imperfecta (Oi)mentioning

confidence: 99%

Age-related Changes in Human Bone Proteoglycan Structure

Grzesik

Frazier

Shapiro

et al. 2002

Journal of Biological Chemistry

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Proteoglycans (PGs) are a family of molecules that undergo extensive post-translational modifications that include addition of glycosaminoglycan (GAG) chains as well as N-and O-linked oligosaccharides to the protein core. PG composition and structure have been reported to alter with age. To test whether the post-translational modifications to PGs can serve as in vitro surrogate end point markers for chronological age, the extent of GAG modifications was determined for PGs derived from normal human bone cells of 14 donors (age range, fetal to 60 years). Isolated cells were steady state radiolabeled with 35 SO 4 2؊ and [ 3 H]GlcN. For biglycan and decorin, iduronate content was linearly correlated with age (increased 1.5؋ between fetal and age 60 years). For the syndecan-like heparan sulfate PG, the N-sulfation of post-natal cells increased over 3.5-fold until reaching a plateau during the 4th decade of life. The amount of O-linked oligosaccharides was also found to decrease as a function of increasing normal donor age, whereas the specific activity of the metabolic precursor pool remained constant regardless of donor age. These age-related changes in post-translational modifications were then used to demonstrate that osteoblasts derived from patients with osteogenesis imperfecta did not exhibit facets of a pre-mature aging, but rather were arrested in a fetallike phenotypic state. A growth matrix rich in thrombospondin altered PG metabolism in osteoblastic cells, resulting in the production and secretion of the fetal-like (rich in O-linked oligosaccharides) forms of decorin and biglycan. This effect was qualitatively different from the effect of transforming growth factor-␤, which predominantly altered GAGs rather than O-linked oligosaccharides. No other Arg-Gly-Asp protein (fibronectin, vitronectin, type I collagen, osteopontin, and bone sialoprotein) showed any detectable effect on PG metabolism in bone cells. These results indicate that a proper matrix stoichiometry is critical for metabolism of PGs.

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Glycosaminoglycans, proteoglycans and aging

Cited by 4 publications

References 146 publications

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Regulation of Collagenase Activities of Human Cathepsins by Glycosaminoglycans

Age-related Changes in Human Bone Proteoglycan Structure

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