Proteoglycans and Sulfated Proteins of Platelets: Characterization and Response to Thrombin and Adp

Schick, Barbara P.; Walsh, Charles J.; Jenkins-West, Tonya

doi:10.1055/s-0038-1643642

Cited by 5 publications

(17 citation statements)

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“…However, a specific class of proteoglycan contains uniformly sized carbohydrate chains (see refs. [22][23][24][25], although the size of glycosaminoglycan chains may change with maturation (26,27), rate of synthesis (28)(29)(30)(31), intracellular concentration of core protein (32)(33)(34), or during cell culture (35,36).…”

Section: Discussionmentioning

confidence: 99%

Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

Sanderson

Bernfield

1988

Proc. Natl. Acad. Sci. U.S.A.

129

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Epithelial cells are organized into either a single layer (simple epithelia) or multiple layers (stratified epithelia). Maintenance of these cellular organizations requires distinct adhesive mechanisms involving many cell surface molecules. One such molecule is a cell surface proteoglycan, named syndecan, that contains both heparan sulfate and chondroitin sulfate chains. This proteoglycan binds cells to fibrillar collagens and fibronectin and thus acts as a receptor for interstitial matrix. The proteoglycan is restricted to the basolateral surface of simple epithelial cells, but is located over the entire surface of stratified epithelial cells, even those surfaces not contacting matrix. We now show that the distinct localization in simple and stratified epithelia correlates with a distinct proteoglycan structure. The proteoglycan from simple epithelia (modal molecular size, 160 kDa) is larger than that from stratified epithelia (modal molecular size, 92 kDa), but their core proteins are identical in size and immunoreactivity. The proteoglycan from simple epithelia has more and larger heparan sulfate and chondroitin sulfate chains than the proteoglycan from stratified epithelia. Thus, the cell surface proteoglycan shows a tissue-specific structural polymorphism due to distinct posttranslational modifications. This polymorphism likely reflects distinct proteoglycan functions in simple and stratified epithelia, potentially meeting the different adhesive requirements of the cells in these different organizations.Epithelial tissues consist of the cells that line the free surfaces of the body. These cells are organized into either of two arrangements: cells in a single layer (simple epithelia) or cells in two or more layers (stratified epithelia). These arrangements reflect the usual functions of these cells, namely transfer of materials across simple epithelia and protection by stratified epithelia. Both of these functions require that the cells adhere to one another and to their underlying extracellular matrix.Several cell surface molecules involved in cell-cell and cell-matrix adhesion on epithelia have been described (see refs. 1-5 Restriction of the proteoglycan to the basolateral cell surface on simple epithelia is consistent with its behavior as a matrix receptor; its localization over the entire cell surface on stratified epithelia is not. This difference raises the possibility that the nature of the proteoglycan in these epithelial types could differ. Therefore, we compared the structure of the cell surface proteoglycan extracted from simple and stratified epithelia, from both tissues and cells in culture, to assess whether its distinct cellular localization correlates with a distinct molecular structure. Part of these data has been published in abstract form (13). MATERIALS AND METHODSCell and Organ Culture. Normal murine mammary gland epithelial cells (passages 13-22) were maintained as described (14). Keratinocytes from newborn mouse skin were isolated and cultured by the method of Hennings et al....

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Section: Discussionmentioning

confidence: 99%

Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

Sanderson

Bernfield

1988

Proc. Natl. Acad. Sci. U.S.A.

129

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“…It is packaged into secretory granules or vesicles in platelets, mast cells, neutrophils and other leukocytes and is secreted upon activation (3). In other cell types such as lymphocytes and hematopoietic tumor cells (7)(8)(9)(10)(11), endothelial cells (4), and uterine decidua (12) it is constitutively secreted along with granule proteins. Serglycin may contain chondroitin sulfate (CS) or heparin chains.…”

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confidence: 99%

Serglycin Constitutively Secreted by Myeloma Plasma Cells Is a Potent Inhibitor of Bone Mineralization in Vitro

Theocharis

Seidel

Børset

et al. 2006

Journal of Biological Chemistry

115

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Although the biological significance of proteoglycans (PGs) has previously been highlighted in multiple myeloma (MM), little is known about serglycin, which is a hematopoietic cell granule PG. In this study, we describe the expression and highly constitutive secretion of serglycin in several MM cell lines. Serglycin messenger RNA was detected in six MM cell lines. PGs were purified from conditioned medium of four MM cell lines, and serglycin substituted with 4-sulfated chondroitin sulfate was identified as the predominant PG. Flow cytometry and confocal microscopy showed that serglycin was also present intracellularly and on the cell surface, and attachment to the cell surface was at least in part dependent on intact glycosaminoglycan side chains. Immunohistochemical staining of bone marrow biopsies showed the presence of serglycin both in benign and malignant plasma cells. Immunoblotting in bone marrow aspirates from a limited number of patients with newly diagnosed MM revealed highly increased levels of serglycin in 30% of the cases. Serglycin isolated from myeloma plasma cells was found to influence the bone mineralization process through inhibition of the crystal growth rate of hydroxyapatite. This rate reduction was attributed to adsorption and further blocking of the active growth sites on the crystal surface. The apparent order of the crystallization reaction was found to be n ‫؍‬ 2, suggesting a surface diffusion-controlled spiral growth mechanism. Our findings suggest that serglycin release is a constitutive process, which may be of fundamental biological importance in the study of MM.

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“…Mice with a gene deletion of an enzyme required for heparin biosynthesis have severe defects in mast cell granules because of the defect in the heparin serglycin glycyosaminoglycan chains (17,18). Serglycins from other hematopoietic cells, endothelial cells, and decidua contain primarily chondroitin sulfate (2,4,8,9,19). The overall structure of the intact proteoglycan, rather than just the nature of the glycyosaminoglycan chains, appears to govern the interactions of the molecule with other proteins such as collagen, fibronectin (9,15), and CD44 (20,21), suggesting that the core protein is important for organizing these interactions.…”

mentioning

confidence: 99%

“…Examination of the 5Ј-flanking sequences of the human and mouse serglycin genes reveals a number of potential elements that could regulate the expression of this gene. The conserved Ϫ1/Ϫ119 region includes a glucocorticoid response element at Ϫ64, a cyclic AMP response element (CRE) 2 half-site at Ϫ70, and an ets site, CAGGAA, at Ϫ80. The CRE site was of interest because of its important role in the regulation of several hematopoietic genes (26,27).…”

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confidence: 99%

Promoter Regulatory Elements and DNase I-hypersensitive Sites Involved in Serglycin Proteoglycan Gene Expression in Human Erythroleukemia, CHRF 288-11, and HL-60 Cells

Schick

Petrushina

Brodbeck

et al. 2001

Journal of Biological Chemistry

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We have compared regulation of the serglycin gene in human erythroleukemia (HEL) and CHRF 288-11 cells, which have megakaryocytic characteristics, with promyelocytic HL-60 cells. Deletion constructs were prepared from the region ؊1123/؉42 to ؊20/؉42, and putative regulatory sites were mutated. In all three cell lines, the two major regulatory elements for constitutive expression were the (؊80)ets site and the cyclic AMP response element (CRE) half-site at ؊70. A protein from HEL and CHRF, but not HL60, nuclear extracts bound to the (-80)ets site. Another protein from all three cell lines bound to the (-70)CRE. Phorbol 12-myristate 13-acetate (PMA) and dibutyryl cyclic AMP (dbcAMP) increased expression of the reporter in HEL cells 2.5-3-and 4.5-fold, respectively, from all constructs except those with (-70)CRE mutations. PMA virtually eliminated expression of serglycin mRNA and promoter constructs, but dbcAMP increased expression in HL-60 cells. The effects of PMA and dbcAMP on promoter expression correlated with mRNA expression. The strengths of two DNase Ihypersensitive sites in the 5-flanking region and the first intron in all three cells correlated with relative endogenous serglycin mRNA expression. An additional DNase I-hypersensitive site in HL60 DNA in the first intron may be related to the high serglycin expression in HL60 relative to HEL or CHRF cells.The serglycin proteoglycan is synthesized by a number of hematopoietic cells, including platelets (1) and their parent megakaryocytes (2), granulocytes, macrophages, and lymphocytes (3-6), mast cells (4), and a large number of hematopoietic tumor cell lines (3, 7-10). Mature erythrocytes do not contain proteoglycans. We have recently found that serglycin is a major component of endothelial (11), murine uterine mesometrial decidual (12), and murine embryonic stem cell proteoglycans. 1Serglycin is thought to be critical for packaging and storage of various proteins in and secretion from hematopoietic cell granules and for modulating their activity. Serglycin binds to and stabilizes the chymases in the protease-containing secretory granules in mast cells (4, 13) and binds to granule-associated cytokines or chemokines such as MIP-1␣ and platelet factor 4 (14). Serglycin can bind to a number of matrix proteins such as fibronectin and collagen (9,15,16) and thus can influence cell/matrix interactions (16). We have reported that the serglycin proteoglycan of platelets of Wistar-Furth rats, which have a severe defect in ␣ granule structure and protein content, has abnormally shortened glycyosaminoglycan chains (15). Mice with a gene deletion of an enzyme required for heparin biosynthesis have severe defects in mast cell granules because of the defect in the heparin serglycin glycyosaminoglycan chains (17,18). Serglycins from other hematopoietic cells, endothelial cells, and decidua contain primarily chondroitin sulfate (2,4,8,9,19). The overall structure of the intact proteoglycan, rather than just the nature of the glycyosaminoglycan chains, appears to govern the ...

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Proteoglycans and Sulfated Proteins of Platelets: Characterization and Response to Thrombin and Adp

Cited by 5 publications

References 0 publications

Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

Serglycin Constitutively Secreted by Myeloma Plasma Cells Is a Potent Inhibitor of Bone Mineralization in Vitro

Promoter Regulatory Elements and DNase I-hypersensitive Sites Involved in Serglycin Proteoglycan Gene Expression in Human Erythroleukemia, CHRF 288-11, and HL-60 Cells

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