Linked Life Data

9010914

Source:http://linkedlifedata.com/resource/pubmed/id/9010914

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-3-25
pubmed:abstractText
Ehlers-Danlos syndrome type VI (EDS VI) is an autosomal recessive disorder of connective tissue characterized by hyperextensible, friable skin and joint hypermobility. Severe scoliosis and ocular fragility are present in some patients. This disease is caused by defective collagen lsyl hydroxylase, a vitamin C-dependent enzyme that converts lysyl residues to hydroxylysine on procollagen peptides. Hydroxylysine is essential for the formation of the covalent pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (Dpyr), among mature collagen molecules. Pyr derives from three hydroxylysyl residues, whereas Dpyr derives from one lysyl and two hydroxylysyl residues. Patients with EDS VI have high urinary excretion of Dpyr, resulting in a high ratio of Dpyr-Pyr. In this study, we evaluate content and production of pyridinium cross-links in the skin and cultured fibroblasts from patients with EDS VI. The skin of normal controls contained both Pyr and Dpyr, with a marked predominance of Pyr as observed in normal urine. The skin of patients with EDS VI had reduced total content of pyridinium cross-links, with the presence of Dpyr but not Pyr. Long-term cultures of control fibroblasts produced both Pyr and Dpyr, with a pattern resembling that of normal skin. By contrast, cross-links were not detected in dermal fibroblasts cultured from patients with EDS VI. Vitamin C, which improves the clinical manifestations of some patients with EDS VI, decreased Dpyr accumulation though only minimally affecting Pyr content in control cells. By contrast, addition of vitamin C to fibroblasts from patients with EDS VI stimulated the formation of Dpyr more than that of Pyr and greatly increased total pyridinium cross-link formation. These results indicate that qualitative and quantitative alterations of pyridinium cross-links occur in skin and in cultured dermal fibroblasts of patients with EDS VI and may be responsible for their abnormal skin findings. The vitamin C-stimulated production of Dpyr and Pyr in fibroblasts from patients with EDS VI may explain at least in part the therapeutic effects of this vitamin in EDS VI.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1081-650X
pubmed:author
pubmed:issnType
Print
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers-Danlos syndrome type VI.
pubmed:affiliation
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't